Talk:Histone acetylation and deacetylation

Controversy Over the Model

I removed this third paragraph from the leading section that someone had left before. There is no citation for the statement made, but i think its an interesting talking point on the validity of the model currently accepted. Is it widely known that there may be a problem with the neutralization model?BigA726 (talk) 01:43, 12 March 2014 (UTC)

"This charge neutralization model has been challenged by recent studies, according to which transcriptionally active genes are correlated with rapid turnover of histone acetylation. This requires that the HATs and HDACs must act continuously on the affected histone tail. Methylation at a specific lysine residue (K4) is involved in _targeting histone tails for continuous acetylation and deacetylation."

Figures

I feel the previous diagram is outdated, so I included a image form our textbook in this page. It is a better representation of the overall structure of nucleosome.Luyao Kevin Xu (talk) 00:48, 25 March 2014 (UTC)

Review from Graeme Bartlett

The article has undergone a significant expansion so I can see work is done. Firstly the image File:Nucleosome Overall Structure.jpg appears to come from a textbook. Copyright almost certainly applies without any permission to have the image here. Really you should draw this your own way.

Remember we are writing for non experts, so when you introduce a new term, such as dsDNA it should be explained even if only double stranded DNA. Links to the other articles on these topics is a good idea. "implicated in transcription" sounds like a crime has taken place.

I reckon that a diagram of the acetyl group on lysine with the reaction would be more helpful that the acetyl skeleton diagram.

When you write about HDACs, expand that acronym to start with. There is an article called HDAC11, but you use HDAC 11, so which is right?

There is a whole series of article called "epigenetics in ...." various things that could be worth linking to. eg Cancer epigenetics. Graeme Bartlett (talk) 11:37, 30 March 2014 (UTC)

Thank you for your input Graeme. I have changed the image that was on the article. I am in the process of finding another suitable image that we can use on the internet. This time I will be sure to consider the copyrights problem. We will look into simplifying the article as we are going to assume readers have no previous knowledge of the topic. We have made some links to some Wikipedia pages(HATs and HDACs). I am also going to a organic chemistry software to draw out lysine to acetyal-lysine so that we can incoperate that into the article as well. Again, thank you for the comments. Please do check back as we are adding more information to the article.Luyao Kevin Xu (talk) 23:15, 5 April 2014 (UTC)

Hi Graeme, I was just following up on the email that i replied to a few days ago asking about other topics you would suggest we include in our article. Thanks!BigA726 (talk) 23:53, 7 April 2014 (UTC)

Comments from Jhayes21

Nice article! I think this is definitely on the right track. First and foremost, the lead section is captivating and has a well chosen picture to entice the reader with, yet even if the lead is the only thing the reader sees, is still informative.

The citations look formatted properly. Another positive is the references used were also varying in publication dates which emphasizes the importance of history but also the present day applications - good work!. One suggestion would be to perhaps find collaborating references so that there aren't entire paragraphs with one source. For instance, in HDACs section, there are 5 paragraphs with 5 citation marks (all steaming from citation 9 or Gallinari, P et al.).

Overall the content is well written, there are few areas where it might be beneficial to "condense" some of the language. For instance, the second paragraph of the lead is:

"Acetylated histones and nucleosomes represent a type of epigenetic tag within chromatin.[3] Acetylation removes the positive charge on the histones, thereby decreasing the interaction of the N termini of histones with the negatively charged phosphate groups of DNA. As a consequence, the condensed chromatin is transformed into a more relaxed structure that is associated with greater levels of gene transcription. This relaxation can be reversed by HDAC activity. Relaxed, transcriptionally active DNA is referred to as euchromatin. More condensed (tightly packed) DNA is referred to as heterochromatin. Condensation can be brought about by processes including deacetylation and methylation; the action of methylation is indirect and has no effect upon charge."

But perhaps changing it to something like this would be beneficial:

"Acetylated histones and nucleosomes represent a type of epigenetic tag within chromatin.[3] Tightly packed DNA referred to as heterochomatin, may undergo acetylation resulting in a diminished interaction of the positively charged histones with the negatively charged N-termini phosphate groups of DNA. Consequentially, an overall conformational change in chromatin from a condensed state (positive and negative charge interaction) to a more relaxed structure (positive charge removed) ensues. This relaxed structure displays greater gene transcription levels and when transcriptionally active is referred to as euchromatin. HATs participate in relaxation, while HDACs can reverse this relaxation."

By immediately and briefly summarizing the pathway, introducing important terminology and then introducing HATS and HDACs, this second lead paragraph is structured by subject reflective of the overall article. Again, this is just an idea to help with clarity to the reader and cohesiveness of the article - feel free to use it or not!

The pathway description is well researched and informative, adding visuals to demonstrate the pathway would be helpful to "break up" the larger bodies of text or perhaps a "summary" visual such as http://journals.prous.com/journals/dof/20073201/html/df320045/images/image01.jpg would help.

Another suggestion would be to find a way to make sub sections in HATs and HDACs - perhaps by class/group/family of enzymes?

Lastly, perhaps trying to continue linking appropriate pages throughout the body of the article? if possible ?

This article has a neutral view point, is well explained, and overall a great start! Jhayes21 (talk) 14:47, 1 April 2014 (UTC)

Hey Jhayes21, thanks so much for the review! You definitely had some great points i overlooked. I'm currently in the process of reading through a couple of my articles so i can compile a few more sources for the HDAC section. In the process i'll probably add a few more sources throughout the article. I looked at the second paragraph of the leading section and came up with a small paragraph. I'd love your opinion on it before i post it!

When DNA is acetylated by HAT enzymes, the DNA becomes loosely packed and more neutral in charge and is known as euchromatin. This relaxed state of the nucleosome complex means transcription machinery can more easily access the DNA which leads to increased levels of gene transcription. When this DNA is acted upon by HDAC enzymes, the histones become more positive which allows them to interact more with the DNA causing a much tighter structure known as heterochromatin. Due to the tight interaction between DNA and histones, transcription machinery cannot access the DNA and leads to gene silencing.

I saw your comment about creating subsections in the HAT/HDAC sections. I think its a great idea and i'll definitely have to try and reorder the information. I didn't want to get too specific into each of the enzyme classes since there are specific pages dedicated to both, but i think by reorganizing it, it may actually help me keep things more organized and cut down a little on extraneous information. Thanks for all your help!BigA726 (talk) 22:51, 6 April 2014 (UTC)

Hey! So i ended up taking a look at the leading section again and decided that the second paragraph is pretty ok. I tried bringing it down a couple of times and found myself using a lot of jargon in small sentences. I felt like if i was a high schooler reading it for the first time, it would probably turn me off to reading the article. Although its slightly long, it draws out the ideas in a way thats easier to take in. Thanks so much for the suggestions though, they really sounded great!BigA726 (talk) 01:35, 9 April 2014 (UTC)

Sorry, forgot to include my main point. I really took to heart your suggestion on reorganizing the article. So i went through the HDAC section first and completely reorganized it by HDAC Class, and then explained each HDAC in sections. That was definitely a great idea and i plan to do the same thing for the HAT section soon. Thanks for your help!!BigA726 (talk) 01:38, 9 April 2014 (UTC)

The lead section looks great! You all have certainly added a lot more! It looks great!! I am glad the reorganization for HDAC and the subsections for HDAC worked out Jhayes21 (talk) 21:34, 6 May 2014 (UTC)

Comments from Misha Subzwari

Good article, very informative!

I have just a few pointers;

To start off, the picture is nice and colorful but it would be nice to see a picture showing what the chromosome looks like acetylated and deactylated, like the picture on this link shows a nice representation (http://cellways.blogspot.com/2012/03/take-two-hdac-inhibitors-and-call-me-in.html).

Maybe mention transcriptional elongation and its importance in acetylation.

The section "pathway" is a bit confusing; pathway to what? pathway for what? maybe expand on the pathway to....same goes for the next section (maybe add, "enzymes involved" in the subtitle).

This paragraph 'mSin3A, NURD/Mi2/NRD and CoREST.. HDAC2 also plays a role in regulating the proapoptotic signals from the WNT pathway that ensue from colon cancer. HDAC1 KO mice die during embryogenesis ' is a bit confusing, not sure what all those acronyms mean.

Make an overall connection and show the bigger picture of histone acetylation in reference to Genome Integrity, DNA Replication & DNA Damage Repair.

its role in alzheimers and maybe mention the latest research on this overwhelming disease and how acetylation is either benificial or harmful.

I would definitely say this is a great start! Mishasubz (talk) 02:54, 2 April 2014 (UTC)

Thank you for commenting Misha. Great suggestion on the image. I was also looking into adding a similar picture in our article. I am writing up about transcription regulation under the biological functions section. And I have also change the titles of some of our sections to make it more clear to the readers. Please check back as we are adding more information! Your comments are very helpful.Luyao Kevin Xu (talk) 23:20, 5 April 2014 (UTC)

Hey Misha! So i took a look at the sections i wrote and thought you had some great points. I went through and tried to explain some of the abbreviations a bit better. Some i still have to find a good explanation for, but i'm definitely trying! Also, i plan on beefing up the pathway section this week, so any issues will be resolved soon. Thanks for your input!!BigA726 (talk) 01:39, 9 April 2014 (UTC)

Introduction

Hi Adam,

I am posting my responses to the article here so everyone can see it and have an idea of how we communicate with each other.

I have read the introduction section and I do think we need to focus on several key points. We do not need to go into detail about how everything works. This is for the following sections. So in my opinion, we should focus on 1.Intro, 2.what is acetylation/deacetylation, 3.what type or family of enzymes are involved?, 4, what are some of the biological functions of this modification? 5, how are this relevant?(this should be just one or two sentences)

I think if we have the 5 key elements pin down in introduction then it will give readers an overview of the article. Then we can elaborate further in the content of the article. What do you think?Luyao Kevin Xu (talk) 02:03, 8 April 2014 (UTC)

I agree, i think that would be a great way of introducing the topic. i'm in the process of redoing my HDAC section. I decided to take Jhayes21's advice and separate the paper in the topic. I think this will clear up the concerns that Mishasubz had when reading the paper. I'll touch up the leading section and hopefully be able to post my revised HDAC section by the end of today. I'll make sure to keep a copy of the old section on my computer just in case there are some points that don't carry over (better safe than sorry haha). I'll definitely keep your suggestions in mind while i'm looking at the leading section. Thanks for the responses!!BigA726 (talk) 17:32, 8 April 2014 (UTC)

Unit 10 progress report

For Unit 10 I have continuously added more content to our article. I have look at the over structure of the article and provided some advice to group member. Following is a list of the items I have added so far. 1. Found a new image that demonstrate the histone acetylation/deacetylation process. I feel it is a good illustration for our article, as it gives readers a clear idea of how histones are modified. 2. I have added more content under the biological functions section. The transcription regulation is almost complete. And the therapeutics part still needs some work. 3. I have read and made changes according to the reviewer's comments. Some of the comments are very helpful and made our article easier to browse through.Luyao Kevin Xu (talk) 01:54, 9 April 2014 (UTC)

Review by Neelix

You have done a lot of great work on this article. Here are some recommendations for how to improve the article further:

1. The lead should explain the meanings of the terms "histone" and "acetylation".
2. All paragraphs should consist of more than one sentence, and all sections should consist of more than one paragraph.
3. There should be no links or bracketed abbreviations in section headings, nor should there be capitalization of common nouns (ex. "Mechanism of Action" should read "Mechanism of action").
4. There is no need to repeat the article title in section headings; "Histone Acetylation/Deacetylation and Human Diseases" can be simplified to "Human diseases".
5. Be careful to avoid allcaps, even in the "References" section.
6. If this article isn't linked in a navbox, then that navbox shouldn't be included in the article.
7. There is no need to duplicate citations in a paragraph in which adjacent sentences derive their information from the same source; a single citation at the end of the last of these sentences covers all of the preceding sentences leading back to the previous differing citation or the beginning of the paragraph (whichever is closest).

I'm impressed by your progress with this article. Feel free to contact me if you have any questions about the suggestions above. Neelix (talk) 04:27, 14 April 2014 (UTC)

Hey Neelix! Thanks so much for the advice on the article and for the kind words! I put a small bit of info into the lead section on histones and acetylation. I also changed the capitalization of some of the section headings. I do have a question about your third point. Should i not link HDAC1 through 11 to their respective pages in those titles? Just in case, i made these changes. I also edited some of the section titles to reduce the amount of redundancy. Also, you mention that we used allcaps. Could you let me know where you saw that? I couldn't find it and i'd definitely like to fix that. I'll also be fixing the citation markings during the day tomorrow. I just wanted to give you a heads up and let you know that i'm in the process of taking care of your suggestions. They're all valid points and i'll definitely try to fit in fixing them all before the deadline tomorrow night. Thanks for your time!BigA726 (talk) 02:03, 15 April 2014 (UTC)

Thanks for the feedback Neelix, your suggestions are very helpful for us. The last section is still under construction, but I will be filling it up as I have more information to put in. I will look at the reference section a little bit closer to avoid duplications.Luyao Kevin Xu (talk) 14:38, 15 April 2014 (UTC)

Review from Tmo32

Overall, I don't have any substantial changes to your content, just a few tweaks here and there to make it an easier read.

Content Coverage

• The article is well written and very informative. It is a vast improvement on the content that was there previously. Nicely done.

Wikilinking

• Decent job of wikilinking so far, but more wikilinks could be included. There is a lot of complex material throughout, but paragraph after paragraph with no wikilinks. Consider including wikilinks for words like "nucleosome", "Lysine", "N-terminus", "condensation", "methylation", "double-stranded DNA", "minor groove", "phosphorylation", etc.

Referencing

• I agree with the previous reviewers that more references should be added. There are long stretches of information with no sources provided.

Writing categories

• To make it an easier read, be mindful of consistency in defining subjects as plural or singular. For instance, you describe histone acetylation and deacetylation as "processes" (plural) in the opening paragraph, but refer to them as "it" (singular) in the next paragraph and then again as "these reactions" (plural) in the next sentence.
• In the HAT section, change affects to effects in the following sentence, "The affects of acetylation lead to a major change in the overall charge of the histone tails."

Illustrations

• Good use of images.

Again, no substantive changes, but why fix it if it isn't broken? Great job! Tmo32 (talk) 02:33, 15 April 2014 (UTC)

Hey Tmo32! Thanks so much for the review. I just wanted to let you know about some of the changes i made in reference to your review. I went ahead and added a lot more wikilinks throughout the article. You made a great point about making sure information is more easily accessible. I made sure to read through the whole article and linked a lot of the more esoteric terms to their respective pages. Some actually dont have individual pages, so i'm still trying to figure out the best way to get around that. In terms of referencing, yes, we're definitely working on getting more references added in. In addition, i went through and cleaned up a lot of my sourcing so that multiple entries weren't in tandem. I also went through and did an overall grammar check. You were right! We did slip up a few times on that, but it should be all fixed for now. I also went and changed affect to effect. Thanks so much for the suggestions!! They were really great and definitely helped out in making the article better!BigA726 (talk) 01:45, 16 April 2014 (UTC)

Thanks for providing feedback on our article Tmo32. We are working on putting more references into the article and will focus on editing the article to make it smooth. Let us know if you have more comments, we will be more than happy to look into things that can improve our article. Luyao Kevin Xu (talk) 18:20, 22 April 2014 (UTC)

Review by SabFernMB

1. It is well-written and nicely organized. The article flows nicely and is easy to follow.
2. It is written in a neutral point of view
3. For Section 2.1 (HAT) you may want to have sub-headings (same as 2.2) for the two superfamilies mentioned. In Paragraph 2 of this section, second sentence, please correct the spelling of “to” to “two”. Please elaborate on how the MYST family functions i.e. does the members of this family function in a similar manner as the PCAFs family members?
4. Histone Code Hypothesis: the sentence “Chemical modification of histone protein occur on particular amino acids, and this specific modification on handful of amino acid, hence the pattern of single or all of the modifications can be interpreted and have functional implications” is not clear – please reword. You may want to provide examples of the amino acids that are modified as well as examples of functional implications.
5. Bromodomain: the sentence “Structural analysis of transcription factors has uncover that the highly conserved bromodomain are essential for acetylated lysine binding” is unclear. You may want to reword as follows “Structural analysis of transcription factors have shown that the highly conserved bromodomain is essential for acetylated lysine binding”.
6. Good use of wikilinks; Additional links you may want to use are catalytic domain (active site), amino acid, Huntington’s disease, schizophrenia
7. References: good start on this section; You may want to provide additional references to support information in each section
8. Illustrations: good examples of the histone structure and Histone acetylation and deacetylation
9. Overall, great job on the article! SabFernMB (talk) 00:58, 16 April 2014 (UTC)

Hey SabFernMB! Thanks for the review! My partner and I have reviewed the article and we think we've fixed up a few of the points you mentioned! I'm going to be going through the article in the next week or so and still add a few more wikilinks. I went back and redid the entire HATs section so that it was a bit more organized from before. I also added a couple of new references. Thanks so much for taking the time to read our article!BigA726 (talk) 01:07, 22 April 2014 (UTC)

Thanks for the comments! We have looked at those things you pointed out and thanks for the wikilinks suggestions. I will incorporate more wikilinks in our article and have more references listed.Luyao Kevin Xu (talk) 18:22, 22 April 2014 (UTC)

Comments from Jocelyn Munson

Great job on the article so far! I have a few suggestions for each section:

Lead Section

• The figure illustrating histone acetylation and deacetylation needs a caption

• Protein infoboxes would be a good addition to this section

• “Given they are an essential part of gene regulation, histone acetylation and deacetylation are highly regulated”. I would remove this sentence, especially since gene regulation was already mentioned.

• The third paragraph (“Acetylated histones…”) should be written more concisely. Defining heterochromatin and euchromatin is a good idea, but the fine details of acetylation do not belong in the lead section (“ Acetylation removes the positive charge on the histones..”) especially since they are mentioned elsewhere in the article.

• The fifth reference (Watson textbook) needs page numbers.

Mechanism of action

• This section is thoroughly written, and has great references. A few minor suggestions:

• The figure illustrating histone acetylation and deacetylation could be moved to this section

• “Not only do the tails insert themselves in the minor grooves of the DNA for support and binding...” This doesn't seem relevant to histone acetylation and deacetylation, and should probably be removed.

Histone acetylation/deacetylation enzymes

• This section is very informative. A table or two briefly summarizing the histone acetylase and deacetylase classes and families would be a great addition for this section. Images would also be good additions.

• In the subsection “HDAC1 & HDAC2” be careful of too-close paraphrasing:

Article: “HDAC1 & HDAC2 are in the first class of HDACs are most closely related to one another[7][8] with a sequence similarity of approximately 82%”

Reference 7 (de Ruijter): “HDAC1 and HDAC2 are highly similar enzymes, with an overall sequence identity of approx. 82%”

Also, those reference links should be at the end of the sentence, not in the middle.

Biological functions

• Do histone acetylases and deacetylases have other functions apart from transcription regulation?

• The subsection “histone code hypothesis” is somewhat confusing. The writing needs to be cleaned up. Also, you mentioned “specific cellular functions”. What are these functions?

Human diseases

• This was pointed out on the article I've been working on. Be aware of the stricter guidelines for referencing sources related to medicine. You should only refer to review articles and they should preferably be from the last five years. Some of your references (i.e.: reference 29) don’t fit those guidelines. in tran

• The first paragraph of this section should have references. Also, elaborate on “novel therapeutic _targets”. What are they?

• Adding a brief introduction that explains how histone acetylation and deacetylation are related to disease would be helpful.

• The “other disorders” section should have subheadings (cardiac hypertrophy, neurological disorders)

As far as I can tell, the references accurately reflect the written content. More wikilinking is needed (RNA polymerase II, myogenesis, basic helix-loop-helix…). I spotted some typos and odd capitalization of words (Lysine, Schizophrenia).

As you go back through the article, try to make it more concise and straightforward. For example, is the mention of mSin3A/YY1 in the “HDAC1 & HDAC2” section relevant? If so, explain mSin3A/YY1 to the reader.

I hope you find my comments helpful. --Jocelyn Munson (talk) 20:10, 28 April 2014 (UTC)

Hey Jocelyn, I went through and fixed up the article a little bit. I fixed the lead section by cutting out some of the mention of gene regulation and making that more concise. I have to disagree on the next point. The lead section is meant to be an overview of the important points of a topic and i feel that charge differences are the main reason that trancription is effected. I agree the picture of the mechanism should be moved down and i informed my partner about it. I fixed the information on histone tails to make it more relevant. I think its important to state how they fit through the DNA. I had really considered adding tables to the articles, but i felt this would be too much of a copy from the HAT and HDAC wiki pages. I fixed one of the sources you pointed out for being in the middle of a sentence, but the reason i do that is because only one of those sources references a fact in the sentence while another source may state a different fact not included in the other paper. I also cleaned up the structure of the sentence so that it was less similar to that found in the article. Thanks so much for pointing that out!! I'll read through the rest of the article and check for any more grammatical or spelling mistakes. Thanks so much for your time!!!BigA726 (talk) 20:00, 29 April 2014 (UTC)

Thank you for your input on our article. I have taken you suggestions and made changes on the diagram and change wording of some parts of the article. For biological functions, the main theme for acetylation/deacetylation is transcription activation. But as stated in the article, it also marks the histone for transcription factor binding via bromodomain. Furthermore, the combination of histone modifications all adds up to suggest the overall role of a coding system. Specific cellular function depends on the gene. Since acetylation/deactylation is a widespread regulatory mechanism, it governs expression of many genes and downstream functions. Regarding reference #29, I agree reviews are better. And I will look into adding a different source.Luyao Kevin Xu (talk) 21:44, 29 April 2014 (UTC)

I added a bunch of new wikilinks, i added our article to the navbox and changed the placement of the mechanism picture as well as fixed grammatical mistakes and spelling errors in the article. Hopefully the edits are helpful. Thanks so much for the suggestions!!BigA726 (talk) 15:23, 3 May 2014 (UTC)

You're welcome! The improvements look good! When I made the comment about adding tables, I hadn't realized that the HAT and HDAC wiki pages already had them. I understand your reasoning for not including them in this article. --Jocelyn Munson (talk) 03:21, 6 May 2014 (UTC)

I have added more wikilinks to my sections and included more secondary sources as you suggested. For all the citations under human disease section, I went through them and exchanged review articles for the primary sources. Thanks again for all your input!Luyao Kevin Xu (talk) 21:36, 6 May 2014 (UTC)

REVIEW FROM KATHERINE BARNHILL

This article has come such a long way, looks great! A few suggestions: incorporate more wikilinks throughout the article and be sure the references are cited correctly and thoroughly. Overall, the article is well written and possessed a neutral tone.

• Lead section: easy to follow and not overwhelming.
• Mechanisms of action: definitely include more wikilinks, for this section is quite technical. There are a few grammatical errors, so watch out for those ("acetylation...in transcriptional regulation, while deacetylation..."--missing the comma)
• Histone enzymes: I like how it's organized and is well written, include more wikilinks
• Biological functions: include more wikilinks, how does the histone code hypothesis pertain to the other information presented in the article?
• Human diseases: very nice, but incorporate more wikilinks

The references appear applicable to the topic! Klbarnhill (talk) 00:18, 29 April 2014 (UTC)

Thanks for all the comments Katherine. We are very happy about the article as it is, but we are planning on making some small changes and adding more information to it. We will for sure work on the wikilinks for each section. Hopefully get a better rating at the end. Thanks again.Luyao Kevin Xu (talk) 21:11, 29 April 2014 (UTC)

Hey Katherine, thanks so much for the review! I'll be going through the article over the next week and fixing up any spelling or grammatical mistakes i come across. I'll definitely look to add more wikilinks as i go. i know i went through and added a bunch, but there were some more esoteric terms that didn't have any wiki pages that existed, so i couldn't, but i'll go through and look for some more that i can add in. Thanks so much for your time!!!BigA726 (talk) 21:33, 29 April 2014 (UTC)

I've taken the time and added a bunch of wikilinks into the article. Its hard to add wikilinks to some of the more esoteric terms since some of them aren't well researched or don't have their own wiki pages. I'll take some more time and see if i can add a couple more, but hopefully my edits help out! Thanks for the suggestions!!BigA726 (talk) 15:21, 3 May 2014 (UTC)

I have also added many wikilinks throughout the last couple sections. Changed many sources to secondary. I have also change the wording of those sentences. The article is much nicer after all these changes. Thank you so much for your comments!Luyao Kevin Xu (talk) 01:17, 7 May 2014 (UTC)

Review from Keilana

Hi everybody, great job so far! Here are some comments for you as you finish out the semester. Let me know on my talk page or via email if you have any questions!

• I really like your use of colored text in the first image caption. That makes things very clear for the reader. One suggestion - since this may be difficult for color-blind readers, you could add alt-text explaining the orientation. Check out WP:ACCESS for more accessibility suggestions. I'm not an accessibility expert, though, and this is difficult to explain because the image is in color as well.
• Usually, we don't use citations in the lead because it should be a summary of everything in the article and it should be cited and discussed elsewhere in the article. The exception is if there's a brief fact that doesn't need to be mentioned anywhere else in the article.
• Great job glossing difficult terms in the lead, that makes the article WAY more accessible to the lay reader. It's totally okay to go into more complex concepts in the body of the article. I think you got that really well.
• In general, the article is really well fleshed out.
• The second bit of the first paragraph in "Transcription regulation" needs a citation. Same with the second paragraph of that section, and the last part of "Bromodomain".
• So, our requirements are a little bit different when it comes to writing about medicine. Most of the article doesn't fall under our medical sourcing guidelines but the section on human diseases does. The two parts that you need to worry about the most are the recency and review requirements. Everything you cite should (ideally) be from the past 5 years and be a review article. Go through your sources for this section and make sure they meet both requirements. If you have trouble finding a replacement source, one thing I find helpful is looking at the papers that cite the paper you originally used - if it's a good paper, it'll be cited in a recent review, and then you can just cite that instead. I know this guideline can be confusing, but it's really important to have recent and review-correlated clinical information on Wikipedia since health professionals often use Wikipedia. Let me know if you have any questions!
• In general, be careful not to draw original conclusions from the research you're citing. When you say, for example, "Theses results, in combination, suggested that there is an important role for HAT/HDAC activity balance in inflammatory lung diseases and provided insights on possible therapeutic _targets", make sure there's a study that says something similar and then cite that study.
• If you can find another relevant image, that would be really great to include.

That's about all I've got. All the best, Keilana|^{Parlez ici} 16:08, 3 May 2014 (UTC)

Hi Keilana. Thank you very much for all the input on our article. I have taken your advice to change the caption of the first diagram we have and changed the colour scheme. This should help make it more accessible. As of the diagram itself, we do not have the source hence there is little we can do.For the citations, I have included some new ones for those places you pointed out and have exchanged the citations for human diseases section. These changes should make our article align with the medical sourcing guidelines. Thank you again for your comments.Luyao Kevin Xu (talk) 21:33, 6 May 2014 (UTC)

Hey Keilana! I just finished making a few edits to the article. I added some content information to the article so as to better improve the subject. I also took the time to remove nearly all the sources from the lead section. There is only one source there and it is for an allusion made to methylation which we dont talk about in this article. Thanks so much for taking the time to review our article and the advice you gave was amazing! It definitely made the article much better!!BigA726 (talk) 00:17, 7 May 2014 (UTC)

Excellent job!

I'm really impressed, especially with the depth of coverage and the amount of content you guys have added. Klortho (talk) 03:35, 9 May 2014 (UTC)