User:BigA726/sandbox

Pillar #1: Wikipedia is an online Encyclopedia

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 * Users of Wikipedia should be bold; include information and challenge information that may be inaccurate, of course always in a pleasant manner. But it is important to remember that not all rules are set in stone. Wikipedia is an ever-changing being that, over time, will change and thus, rules should change as well. But we must keep in mind respect for others and always assure that all information is accurate and up to date.

= Myostatin =


 * Myostatin, a member of the transforming growth factor Beta (TGF-B) family, was discovered by Alex McPherron and Se-Jin Lee. In mice, during embroygenesis, Myostatin was found in the myotomes of somites while adults showed Myostatin levels in all skeletal muscle. Myostatin is a soluble protein which naturally regulates the growth of skeletal muscle. In experiments performed by Se-Jin Lee and Alexandra McPherron, it was found that Myostatin null mice had increased muscle growth due to both hyperplasia and hypertrophy. Experiments indicate that Myostatin functions as a negative muscle regulator. Muscle weights of the null mice were approximately 2-3 times the weight of normal mice . Myostatin deficiency occurs naturally in species such as the Belgian Blue cattle and the Piedmontese cattle . The experiments with mice and natural occurrences of Myostatin null cattle have shown that Myostatin is a negative regulator for the maintenance of skeletal muscle.

=Unit 7 Wiki Assignment=

I found a couple of articles that i think could really benefit us. Unfortunately, some of the ones i really thought would be good, we would have to pay for (at least through pubmed). I'm going to search around tomorrow to see if there are any free versions available. The free ones i though would be good that are free are:


 * 1)Control of Cardiac Growth by Histone Acetylation/Deacetylation - I think its a great starting article. It sounds like it has a lot of preliminary information that would be useful in describing some of the major functions of histone acetylation/deacetylation. I think it'd also be a great article to connect our article to some clinical applications.


 * 2)Localized Histone Acetylation and Deacetylation Triggered by the Homologous Recombination Pathway of Double-Strand DNA Repair - This would be a great article outlining how histone acetylation/deacetylation would be affected by double stranded breaks, recombination and possibly mutations.


 * 3)A Comprehensive Synthetic Genetic Interaction Network Governing Yeast Histone Acetylation and Deacetylation - Working into the article differences and similarities between different organisms would be interesting. Specifying how this process affects yeast could add an additional section. (I think i found another article detailing the process in plants).


 * 4)Reversible Histone Acetylation and Deacetylation Mediate Genome-Wide, Promoter-Dependent and Locus-Specific Changes in Gene Expression During Plant Development - (I found the one detailing the process in plants).

I did find some articles that i think would make an awesome addition to our article, but on pubmed you have to pay to see them. I'll try and find another source tomorrow, but the articles i found are:


 * 1)DNA Methyltransferase 1(DNMT1) Induced the Expression of Suppressors of Cytokine Signaling3 (Socs3) in a Mouse Model of Asthma - This would have been great for adding information on suppressors and on overall function


 * 2)Epigenetic Histone Acetylation and Deacetylation Mechanisms in Experimental Models of Neurodegenerative Disorders - I think a section on Epigenetics would really benefit our article. I personally like neuroscience, so i thought it'd be a nice way of incorporating that into maybe the clinical application section as well


 * 3)Functions of Site-Specific Histone Acetylation and Deacetylation - Another article on the major functioning. I think it'd be good for a section on the mechanism or pathway of our article subject

I found some additional articles, but they have no information on whether they're free or not (they dont even include their abstracts), but based on their titles, they sound like they could contain some really good information:


 * 1)Histone Acetylation/Deacetylation as a Regulator of Cell Cycle Gene Expression.


 * 2)Control of Cardiac Hypertrophy and Heart Failure by Histone Acetylation/Deacetylation - The author of this article is one of the authors on the previous cardiac article i found in the free section. I'm not sure how much the articles would differ, but i think it'd be nice to know in case they find any other supporting evidence we could include


 * 3)The Relation of Histone Acetylation/Deacetylation and DNA Methylation - I think it'd be interesting to include other modifications that take place on the histone tails, possibly in another section to describe and compare how the systems work together

I looked at the article and saw that we actually have a really nice lead section already written. I'm a little hesitant about including the last paragraph though. I read in the manual that we should possible stay away from conflicting arguments in the lead section, so i think an argument against the major model would possibly be better someplace else. I was thinking a Controversey section would be a great way to end the article. So overall, i think a few sections we should include would be a Pathway/Mechanism section. This would be a great place for a major description of what happens and possibly a nice detailed picture on what happens. I find visual representations invaluable when studying this kind of stuff. Another section we could have after that would be a HAT/HDAC section. We could describe a lot of the different factors that come into play while this process is taking place. Clinical Significance would also be a great section to have, possibly near the end of the article as a sort of "sum up" of what the article had to say and how to apply that to real life. An Epigenetics section would be great, possible after the mechanism and HAT/HDAC sections as a way of tying all of the molecular biology stuff together. I included a methylation article title (i think one of the ones i wasn't sure how to get at) above because i think a great section could possible be something like Other Modifications where we discuss some of the other modifications in short descriptions and maybe describe how they affect acetylation and deacetylation. Another good section to include could possible be a Yeast/Plant section (obviously with a better section name). I have an article each for Yeast and for Plant Development, so i think they'd be an interesting section to include.

What other sections do you think we should include? If you liked some of my sections i thought up, are there any specific orders that you'd like to see them?BigA726 (talk) 00:36, 10 March 2014 (UTC)
 * Looks good. I think it makes sense to have the general pictures of the topic first before we go into difference diseases (cancer, cardiac, etc.). Lets focus on acetylation/deacetylation mechanism. My plan is to have a overview of chromatin structure first, and explain a little bit of different modifications, then we can go into the importance of acetylation changes in different diseases/species. I am going to look up some reviews on the topic and post them here. Let me know your thoughts on the overall structure.(talk) 01:46, 10 March 2014 (UTC)
 * I do think we should stay neutral on the topic. And it is best to present all the findings, and not take sides. I am organizing the sections in a different section. Feel Free to add on anything you think may be helpful.Luyao Kevin Xu (talk) 16:28, 10 March 2014 (UTC)

=Overall Structure=

Introduction

Take a look at this article. I think it is a excellent overview on the topic. And this diagram is a good representation of the overall remodeling proteins.

Mechanism/signaling pathways (HAT/HDAC)

On top of your list I think the following papers are very good at describing the mechanisms.

Important role in human diseases

Here we can talk about different diseases (transcription, cancer, cardiac, inflammatory diseases, lipid metabolism , etc)

Therapeutics

Here we can talk about targeting different proteins in diseases. We can mention specific inhibitors and their functions and how successful they are. Any drugs on the market already? Any in development?

Role in other species

Here we can talk about plant/ yeast and how they are models for research


 * Taking a look at what we've both posted, i think a good outline should include a Leading Section first. Its required, so it's the best place for an overview of the article. After the TOC, i think the first section should be a Pathway/Mechanism section. Here, we'll introduce the functions and effects of HATs and HDACs and we can give a pathway and picture of what and how it all happens. I think it'd be a good idea to research a lot of different HATs and HDACs and compile a table almost. There are probably other articles already written about them so it'd be easy to link to them. I think it'd be an important feature for people trying to identify if certain factors would be HATs or HDACs and if so, what they do and how they do it. The next section should probably be an Epigenetics section. It'd be important in tying acetylation and deacetylation into the bigger picture. By doing that, it can easily open into a section on Role in Human Diseases. I think its a great idea to include this, and by starting with an epigenetics section, it'll be an easy lead to. The Therapeutics section is also a great idea, but do you think that'd be better as a subsection in the Role in Human Diseases section? In other words, do you think it'd be a section that could stand on its own, or would the information lean too closely on its previous section? After these sections, we should definitely go with Roles in Other Species. With the articles i found (and possible a few more) it'd be easy to get a good idea of how acetylation and deacetylation affect other species. I did see in the leading section we have now that the last paragraph talks about controversies. I dont think thats appropriate for a leading section, but i do think it'd be interesting to look into the article the person who wrote that cited it with. It could be a potential Controversies section as our final section. It'd be a good place to inform readers on other models that may exist or possible problems that may exist with the current one. I'll remove the last paragraph for now and put it in the talk section and see what others think about it. If we decide it is important enough, we can always add it in again later. Does this outline sound good to you? So the preliminary outline would be:
 * Leading Section
 * Table of Contents
 * Pathway/Mechanism
 * Table of HATs and HDACs (possibly)
 * Epigenetics
 * Role in Human Diseases
 * Therapeutics (Maybe make it its own section)
 * Roles in Other Species
 * Controversies

Also, i'm not quite sure i've got the hang of the images thing yet, but i used the search function and found two good pictures that could help in some of our explanations. The first is http://upload.wikimedia.org/wikipedia/commons/8/8a/Nucleosome_structure.png this would be a good schematic for detailing a histone. The next is http://upload.wikimedia.org/wikipedia/commons/2/22/Normal-cancer-epigenome.png I know we had mentioned tying our subject into cancer. If we were to do that, this may be a good image to help us make our point! BigA726 (talk) 01:54, 12 March 2014 (UTC)

Notes for Article
Nucleosomes are portions of dsDNA that are wrapped around protein complexes called histone cores. These histone cores are composed of 8 subunits, two each of H2A, H2B, H3 and H4 histones. This protein complex forms a cylindrical shape that dsDNA wraps around with approximately 146 base pairs. Nucleosomes are formed as a beginning step for DNA compaction that also participate in structural support as well as serving functional roles (Verdone). These functional roles are contributed by the tails of the histone subunits. Not only do the tails [intercalate or insert, is that the right word???] themselves in the minor [and major???] grooves of the DNA for support and binding (Book-227-228), but modification of the histone tails have been implicated in transcription (Kuo). Acetylation has been closely associated with increases in transcriptional activation while deacetylation has been linked with transcriptional deactivation [gene silencing???]. These reactions occur post-translation and are reversible (Kuo).

The mechanism for acetylation and deacetylation takes place on the NH3+ groups of Lysine amino acid residues. These residues are located on the tails of histones that make up the nucleosome of packaged dsDNA. The process is aided by factors known as Histone Acetyltransferases (HATs). HAT molecules facilitate the transfer of an acetyl group from a molecule of Acetyl Coenzyme-A (Acetyl-CoA) to the NH3+ group on Lysine. When a Lysine is deacetylated, factors known as Histone Deacetylases (HDACs) catalyze the removal of the acetyl group with a molecule of H2O (Kuo).

Acetylation has the effect of changing the overall charge of the histone tail from positive to neutral. Nucleosome formation is dependent on the positive charges of the H4 histones and the negative charge on the surface of H2A histone fold domains. Acetylation of the histone tails disrupts this association, leading to weaker binding of the nucleosomal components (Text Book-pg 243-244).

Acetylation also increases the affinity of the tails for proteins that contain bromodomains which ... (Book - 668) ????? BigA726 (talk) 01:39, 18 March 2014 (UTC)