H3K9me2

H3K9me2 is an epigenetic modification to the DNA packaging protein Histone H3. It is a mark that indicates the di-methylation at the 9th lysine residue of the histone H3 protein. H3K9me2 is strongly associated with transcriptional repression.[1][2][3] H3K9me2 levels are higher at silent compared to active genes in a 10kb region surrounding the transcriptional start site.[4] H3K9me2 represses gene expression both passively, by prohibiting acetylation[5] as therefore binding of RNA polymerase or its regulatory factors, and actively, by recruiting transcriptional repressors.[6][7] H3K9me2 has also been found in megabase blocks, termed Large Organised Chromatin K9 domains (LOCKS), which are primarily located within gene-sparse regions but also encompass genic and intergenic intervals.[8][9][10][11] Its synthesis is catalyzed by G9a, G9a-like protein, and PRDM2.[1][3][12] H3K9me2 can be removed by a wide range of histone lysine demethylases (KDMs) including KDM1, KDM3, KDM4 and KDM7 family members.[13][6] H3K9me2 is important for various biological processes including cell lineage commitment,[10][14] the reprogramming of somatic cells to induced pluripotent stem cells,[15] regulation of the inflammatory response,[16][17] and addiction to drug use.[2][18][19][20]

  1. ^ a b "H3K9me2". HIstome: The Histone Infobase. Archived from the original on 12 June 2018. Retrieved 8 June 2018.
  2. ^ a b Cite error: The named reference Nestler1 was invoked but never defined (see the help page).
  3. ^ a b Nestler EJ (August 2015). "Role of the Brain's Reward Circuitry in Depression: Transcriptional Mechanisms". International Review of Neurobiology. 124: 151–70. doi:10.1016/bs.irn.2015.07.003. PMC 4690450. PMID 26472529. Chronic social defeat stress decreases expression of G9a and GLP (G9a-like protein), two histone methyltransferases that catalyze the dimethylation of Lys9 of histone H3 (H3K9me2) (Covington et al., 2011), a mark associated with gene repression.
  4. ^ Barski A, Cuddapah S, Cui K, Roh TY, Schones DE, Wang Z, et al. (May 2007). "High-resolution profiling of histone methylations in the human genome". Cell. 129 (4): 823–37. doi:10.1016/j.cell.2007.05.009. PMID 17512414.
  5. ^ Wang Z, Zang C, Rosenfeld JA, Schones DE, Barski A, Cuddapah S, et al. (July 2008). "Combinatorial patterns of histone acetylations and methylations in the human genome". Nature Genetics. 40 (7): 897–903. doi:10.1038/ng.154. PMC 2769248. PMID 18552846.
  6. ^ a b Shinkai Y, Tachibana M (April 2011). "H3K9 methyltransferase G9a and the related molecule GLP". Genes & Development. 25 (8): 781–8. doi:10.1101/gad.2027411. PMC 3078703. PMID 21498567.
  7. ^ Zhang T, Termanis A, Özkan B, Bao XX, Culley J, de Lima Alves F, et al. (April 2016). "G9a/GLP Complex Maintains Imprinted DNA Methylation in Embryonic Stem Cells". Cell Reports. 15 (1): 77–85. doi:10.1016/j.celrep.2016.03.007. PMC 4826439. PMID 27052169.
  8. ^ Filion GJ, van Steensel B (January 2010). "Reassessing the abundance of H3K9me2 chromatin domains in embryonic stem cells". Nature Genetics. 42 (1): 4, author reply 5–6. doi:10.1038/ng0110-4. PMID 20037608.
  9. ^ McDonald OG, Wu H, Timp W, Doi A, Feinberg AP (July 2011). "Genome-scale epigenetic reprogramming during epithelial-to-mesenchymal transition". Nature Structural & Molecular Biology. 18 (8): 867–74. doi:10.1038/nsmb.2084. PMC 3150339. PMID 21725293.
  10. ^ a b Wen B, Wu H, Shinkai Y, Irizarry RA, Feinberg AP (February 2009). "Large histone H3 lysine 9 dimethylated chromatin blocks distinguish differentiated from embryonic stem cells". Nature Genetics. 41 (2): 246–50. doi:10.1038/ng.297. PMC 2632725. PMID 19151716.
  11. ^ Jørgensen HF, Fisher AG (March 2009). "LOCKing in Cellular Potential". Cell Stem Cell. 4 (3): 192–4. doi:10.1016/j.stem.2009.02.007. PMID 19265653.
  12. ^ "Histone-lysine N-methyltransferase, H3 lysine-9 specific 3". HIstome: The Histone Infobase. Archived from the original on 12 June 2018. Retrieved 8 June 2018.
  13. ^ Cloos PA, Christensen J, Agger K, Helin K (May 2008). "Erasing the methyl mark: histone demethylases at the center of cellular differentiation and disease". Genes & Development. 22 (9): 1115–40. doi:10.1101/gad.1652908. PMC 2732404. PMID 18451103.
  14. ^ Chen X, Skutt-Kakaria K, Davison J, Ou YL, Choi E, Malik P, et al. (November 2012). "G9a/GLP-dependent histone H3K9me2 patterning during human hematopoietic stem cell lineage commitment". Genes & Development. 26 (22): 2499–511. doi:10.1101/gad.200329.112. PMC 3505820. PMID 23105005.
  15. ^ Rodriguez-Madoz JR, San Jose-Eneriz E, Rabal O, Zapata-Linares N, Miranda E, Rodriguez S, et al. (2017). "Reversible dual inhibitor against G9a and DNMT1 improves human iPSC derivation enhancing MET and facilitating transcription factor engagement to the genome". PLOS ONE. 12 (12): e0190275. Bibcode:2017PLoSO..1290275R. doi:10.1371/journal.pone.0190275. PMC 5744984. PMID 29281720.
  16. ^ Harman JL, Dobnikar L, Chappell J, Stokell BG, Dalby A, Foote K, et al. (November 2019). "Epigenetic Regulation of Vascular Smooth Muscle Cells by Histone H3 Lysine 9 Dimethylation Attenuates Target Gene-Induction by Inflammatory Signaling". Arteriosclerosis, Thrombosis, and Vascular Biology. 39 (11): 2289–2302. doi:10.1161/ATVBAHA.119.312765. PMC 6818986. PMID 31434493.
  17. ^ Fang TC, Schaefer U, Mecklenbrauker I, Stienen A, Dewell S, Chen MS, et al. (April 2012). "Histone H3 lysine 9 di-methylation as an epigenetic signature of the interferon response". The Journal of Experimental Medicine. 209 (4): 661–9. doi:10.1084/jem.20112343. PMC 3328357. PMID 22412156.
  18. ^ Cite error: The named reference Nestler 2014 epigenetics was invoked but never defined (see the help page).
  19. ^ Cite error: The named reference G9a reverses ΔFosB plasticity was invoked but never defined (see the help page).
  20. ^ Cite error: The named reference HDACi-induced G9a+H3K9me2 primary source was invoked but never defined (see the help page).

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