User:AAR3643/Epigenetic regulation of neurogenesis
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Article Draft
Lead
I am proposing to make edits to the article Epigenetic regulation of neurogenesis. This article is rated as start-class on the article's talk page and as such there were various changes that I wished to make to improve the overall breadth of information covered by the article. In particular, while there is relatively decent coverage of information within this article regarding epigenetic factors involved in embryonic neurogenesis, the information regarding adult neurogenesis is rather lacking in depth, and includes many topics that are essentially thrown in randomly without being discussed. For example, one of the changes I proposed was adding an explanation of HDAC and HAT activity into the "histone modifications" subtopic as well as expanding the subtopic to include more than simply the effects of histone deacetylation alone, as is present in the original article. Upon reading the review article, other histone modifications are vital in the regulation of adult neurogenesis, and as such, I believe their inclusion within this article would be essential in ameliorating a few of its shortcomings. In addition, I would also like to expand the discussions on both the miRNA and methylation-specific effects on neurogenesis, as the article discusses them briefly using only one to two sources each to support their arguments. Furthermore, I would also like to add a few more subtopics under "epigenetic misregulation and neurological disorders." The topic itself mentions epigenetic effects of Parkinson's disease, Alzheimer's disease, schizophrenia and bipolar disease, however only contains one subtopic discussing Alzheimer's disease alone. I believe that it would be beneficial for the depth of the article to include information regarding the epigenetic effects of the other diseases as well and provide subtopics for each, utilizing other review articles I had researched but were not included in this proposal.
Article body
Histone modification (edit)
Histone acetylation, deacetylation, as well as the inhbition of histone deacetylation mechanisms also play large roles in the proliferation and self-renewal of post-natal neural stem cells, in contrasting ways. Neural-expressed HDACs interact with Tlx, an essential neural stem cell regulator, to suppress TLX target genes. This includes the cyclin-dependent kinase inhibitor P21 and the tumor suppressor gene Pten to promote neural stem cell proliferation.[1] The most prominently studied and well-understood regulators of chromatin remodeling, which play an important role in adult neurogenesis are histone acetyltransferases (HATs) and histone deacetylases (HDACs). HATs add acetyl groups to nucleosomes, while HDACs remove them. The acetylation of histones leads to decreased condensation of the nucleosomes to target DNA, and increases the likelihood that gene expression may occur by freeing up the DNA targets to bind to their respective transcriptional factors. This process is involved in neural proliferation regulation, as different neuronal cell genes are expressed and repressed. Deacetylation of histones leads to the reverse, and increases the likelihood for the repression of gene expression. HDAC inhibitors (HDACi), such as valproic acid (VPA) and trichostatin A can promote proliferation of adult neurogenesis through the reversal of HDAC activity, inducing differentiation of adult progenitor cells.[2] Inhibition of HDACS by the antiepileptic drug valproic acid induces neuronal differentiation as in embryonic neurogenesis, but also inhibits glial cell differentiation of adult neural stem cells. This is likely mediated through upregulation of neuronal specific genes such as the neurogeneic basic helix-loop-helix transcription factors NEUROD, NEUROGENENIN1, and Math1. Conditional loss of HDAC1, HDAC2 in neural progenitor cells prevented them from differentiating into neurons and their loss in oligodendrytic progenitor cells disrupted oligodendrocyte formations, suggesting that histone deacetlyation plays important but varying roles in different stages of neuronal development.[1]
References
[2.] Hsieh, J., & Zhao, X. (2016). Genetics and epigenetics in adult neurogenesis. Cold Spring Harbor Perspectives in Biology, 8(6). https://doi.org/10.1101/cshperspect.a018911
*note: source 1 below is from the original article, included to cite the information already present within the article*
- ^ a b Hu, X.L.; Wang, Y.; Shen, Q. (2012). "Epigenetic control on cell fate choice in neural stem cells". Protein & Cell. 3 (4): 278–290. doi:10.1007/s13238-012-2916-6. PMC 4729703. PMID 22549586.
- ^ Hsieh, Jenny; Zhao, Xinyu (2016). "Genetics and Epigenetics in Adult Neurogenesis". Cold Spring Harbor Perspectives in Biology. 8 (6): a018911. doi:10.1101/cshperspect.a018911. ISSN 1943-0264. PMC 4888816. PMID 27143699.
{{cite journal}}: CS1 maint: PMC format (link)