User:Sbreedon/sandbox

Article Evaluation
I chose to evaluate the Wikipedia article "Meiosis".

My brief observations about the article:
 * All of the information in the article appears to be relevant to the topic


 * The article appears to be a neutral stating a facts


 * The lead-in is quite long, it should be shortened and all in-depth detail should be stated in the body of the article)


 * Reference articles are relatively recent, but a few are quite old and should be checked for reliability


 * Most of the lead-in has no references but contains a lot of information that should be cited


 * No references in the “overview” section of the article


 * The “history” section should cite the research it is mentioning


 * Citations are needed throughout the “occurrence in eukaryotic life cycles” section


 * Most of the article needs citations
 * The diagrams appear to be correct and relatively easy to understand
 * I checked some of the research journal reference links and all the ones that I tried worked (none of the links were broken and they linked to the correct paper)

Adding Citations
I added a citation to the meiosis article.

Possible Article Topics

 * Coding strand
 * Uniparental disomy
 * Null allele
 * A-site
 * Anaphase lag
 * Coactivator*

Original Article
A coactivator is a protein that increases gene expression by binding to an activator (transcription factor) which contains a DNA binding domain

The coactivator can enhances transcription initiation by stabilizing the formation of the RNA polymerase holoenzyme enabling faster clearance of the promoter. Coactivators may control many other substeps of transcription, including elongation, RNA splicing, and termination and degradation of the coactivator-activator complex.

Some coactivators possess intrinsic histone acetyltransferase (HAT) activity, which acetylates histones and causes chromatin to relax in a limited region allowing increased access to the DNA. CBP and p300 are examples of coactivators with HAT activity. Numerous other enzyme activities have been reported among the 300 known coactivators for nuclear receptors. The most well known of these are SRC-1, SRC-2, and SRC-3. Coactivators work in high molecular weight complexes of 6-10 coactivator and coactivator-associated proteins (termed co-coactivators).

The same coactivator will likely be used to increase transcription of many different genes, since it is the activator that provides the specificity to a particular sequence. Recent evidence indicates that coactivators may have diverse roles outside transcription and that they may act as 'master genes' for regulating major cellular and metabolic growth processes.

In humans several dozen to several hundred coactivators are known, depending on the level of confidence with which the characterisation of a protein as a coactivator can be made.

Copied from Coactivator (genetics)

Potential References
http://www.sciencedirect.com/topics/biochemistry-genetics-and-molecular-biology/coactivator-genetics

Possible Changes

 * possibly merge coactivation (transcription)

Draft Article
Note: things in "[ ]" are notes to myself

[lead in paragraph]
A coactivator is a type of transcriptional coregulator that binds to an activator (transcription factor) to increase the rate of transcription of a gene or set of genes. The activator contains a DNA binding domain that binds either to a DNA promoter site or a specific DNA regulatory sequence called an enhancer. Binding of the activator-coactivator complex to the enhancer site initiates transcription through the recruitment of transcription machinery to the promoter and therefore increases gene expression. The use of activators and coactivators allows for highly specific expression of certain genes depending on cell type and developmental stage.

Activators are found in all living organisms, but coactivator proteins are typically only found in eukaryotes because they are more complex and require a more intricate mechanism for gene regulation. In eukaryotes, coactivators are usually proteins that are localized in the nucleus.

Some coactivators also have histone acetyltransferase (HAT) activity. HATs form large multiprotein complexes that weaken the association of histones to DNA by acetylating the N-terminal histone tail. This provides more space for the transcription machinery to bind to the promoter, therefore increasing gene expression.

Mechanism
Some coactivators indirectly regulate gene expression by binding to an activator and inducing a conformational change that then allows the activator to bind to the DNA enhancer or promoter sequence. Once the activator-coactivator complex binds to the enhancer, RNA polymerase II and other general transcription machinery are recruited and transcription begins.

Histone acetyltransferase (HAT) activity [subheading of mechanism]
Some coactivators also have histone acetyltransferase (HAT) activity meaning that they can acetylate specific lysine residues on the N-terminal tails of histones. In this method, an activator binds to an enhancer site and recruits a HAT complex that then acetylates nucleosomal promoter-bound histones by neutralizing the positively charge lysine residues. The less positivity charged histones then have a weaker bond to the negatively charged DNA, relaxing the chromatin and allowing the binding of other transcription factors and/or transcription machinery to bind to the promoter, thus initiating transcription. Acetylation by HAT complexes may also serve to keep chromatin open throughout the process of elongation, helping to speed up transcription.

N-terminal histone tail acetylation is one of the most common protein modifications in eukaryotes, with about 85% of all human proteins being acetylated. Acetylation is crucial for synthesis, stability, function, regulation and localization of proteins and RNA transcripts.

HATs function similarly to N-terminal acetyltransferases (NATs) but their acetylation is reversible unlike in NATs. HAT mediated histone acetylation is reversed using histone deactetylase (HDAC), which removes the acetyl group from the histones. This causes the chromatin to close back up from their relaxed state making it difficult for the transcription machinery to bind to the promoter, thus repressing gene expression.

Corepression [subheading of mechanism]
Many coactivators also act as corepressors under certain circumstances. Cofactors such as TAF1, BTAF1 and NC2 can generally initiate transcription in the presence of an activator (act as a coactivator) and repress basal transcription in the absence of an activator (act as a corepressor).

Known coactivators [alphabetize list]
There are more than 300 known coregulators to date. Examples of some coactivators include [  ]:
 * SCR-1
 * GRIP-1
 * CBP
 * p300
 * PCAF
 * hTAFII250
 * TFIIIC
 * ACTR/p/CIP
 * UBE3A
 * SWI/SNF/BRG-1 complex
 * CARM-1
 * PRMT-1
 * SRA
 * CDC25B
 * p72
 * SAGA
 * ATAC
 * Mediator (a multiprotein complex)
 * CPB



Biological and clinical significance
Transcriptional regulation is one of the most common ways for an organism to alter gene expression. The use of activation and coactivation allows for greater control over when, where and how much of a protein is produced. This enables each cell to be able to respond to environmental/physiological changes relatively quickly.

Mutations to the genes encoding coactivators leading to amorphic or neomorphic proteins have been linked to diseases and disorders such as birth defects, cancer (especially hormone dependent cancers), neurodevelopmental disorders and intellectual disability (ID) among many others. Dysregulation leading to the over- or under-expression of coactivators can detrimentally interact with many drugs (especially anti-hormone drugs) and has been implicated in cancer, fertility issues and neurodevelopmental and neuropsychiatric disorders.

Coactivators are promising targets for drug therapies in the treatment of cancer, metabolic disorder, cardiovascular disease and type 2 diabetes, along with many other disorders. For example, SCR-3 is often overexpressed in breast cancer, so the development of an inhibitor molecule that targets this coactivator could be used as a potential drug therapy for breast cancer.

Notes for wiki article

 * edit page and figures
 * add full names and functions to coactivator list
 * maybe add some drugs that target coactivators