HAT KAT3 HDAC HDAC KMT KMT PRMT PRMT KDM H3K9me3 H3K4me3 H3K27me3 H3K36me1,2 ASH2L: important for trymetilation of H3 K4 MEN1 MEN1 MEN1 Molecular regulation of H3K4 trimethylation by ASH2L, a shared subunit of MLL complexes Melissa M Steward1, Jung-Shin Lee1, Aisling O’Donovan2,Matt Wyatt1, Bradley E Bernstein2 & Ali Shilatifard1,3 SEPTEMBER 2006 NATURE STRUCTURAL & MOLECULAR BIOLOGY Mistargeting of chromatin modifications occur as epigenetic lesions at MLL-AF4 target regions Guenther M. G. et.al. Genes Dev. 2008;22:3403-3408 ©2008 by Cold Spring Harbor Laboratory Press Model of MLL-AF4-mediated gene activation in leukemia Guenther M. G. et.al. Genes Dev. 2008;22:3403-3408 ©2008 by Cold Spring Harbor Laboratory Press Figure 1. Model in which PRC2 responds to the chromatin environment to establish H3K27me domains. Repressive features of constitutive heterochromatin including DNA methylation (5mC), H3K9me (K9me), and HP1 binding influence methylation of H3K27 by PRC2. Conver... Elizabeth T Wiles, Eric U Selker H3K27 methylation: a promiscuous repressive chromatin mark Current Opinion in Genetics & Development, Volume 43, 2017, 31–37 Fig. 1. Evolution of PcG family. Expansion of the Polycomb genes occurs in vertebrates as the genome size increases. Katelyn E. Connelly, Emily C. Dykhuizen Compositional and functional diversity of canonical PRC1 complexes in mammals Biochimica et Biophysica Acta (BBA) - Gene Regulatory Mechanisms, Volume 1860, Issue 2, 2017, 233–245 http://dx.doi.org/10.1016/j.bbagrm.2016.12.006 Human polycomb complexes functionally interact to regulate histone H3K27 methylation and histone H2A K119 ubiquitination. Emily C. Chittock et al. Biochm. Soc. Trans. 2017;45:193205 ©2017 by Portland Press Ltd Figure 1. Schematic representation of the various classes of PRC1 complexes. (A) Except for PCGF components, subunits are represented in a simplified manner that precludes description of paralogs. Protein–protein contacts are not meant to be accurate in all ca... Miguel Vidal, Katarzina Starowicz Polycomb complexes PRC1 and their function in hematopoiesis Experimental Hematology, Volume 48, 2017, 12–31 The PRC1. Emily C. Chittock et al. Biochm. Soc. Trans. 2017;45:193205 ©2017 by Portland Press Ltd SUZ12 Colon Prostate Colon Breast Breast Skin Liver Lymphoma Liver Myeloma Endometrial Bladder Lung Gastric EZH2 Proteins Drosophila melanogaster Protein domains Human Mouse ESC EED EED WD40 repeats* E(Z) EZH1 EZH1/ENX2 SET domain‡ EZH2 EZH2/ENX1 SUZ12 SUZ12 Zinc-finger domain CBX2/HPC1 CBX2/M33 Chromodomain CBX4/HPC2 CBX4/MPC2 CBX8/HPC3 CBX8/PC3 EDR1/HPH1 EDR1/MPH1/RAE28 EDR2/HPH2 EDR2/MPH2 EDR3/HPH3 EDR3 RING1/RNF1/RING1A RING1/RING1A RNF2/RING1B RNF2/RING1B BMI1 BMI1 RNF110/ZFP144/ PCGF2 RNF110/ZFP144/MEL18 ZNF134 ZNF134 YY1 YY1 Functions PRC2 initiation complex SU(Z)12 Histone methyltransferase PRC1 maintenance complex PC PH RING PSC PHO Methyl-lysine binding Zinc-finger SPM domain§ RING-finger domain|| Ubiquitin ligase RING-finger domain|| Zinc-finger domain PHO-like Sequence-specific DNA binding DNA binding SCM SCML1 SCMH1 Zinc-finger SPM domain§ PCL PHF1 PHF1/PCL1 PHD-finger domain Global perturbations of histones PTMs in human cancers. H4K20me3 Lymphoma mouse SCC Fraga et al. Nat Genet. 2005. H4K16ac (MOF) Lymphoma Breast, Medulloblastoma Fraga et al. Nat Genet. 2005. H3K4me2 (MLL) Prostate Seligson et al. Nature. 2005. H3K18ac Prostate Seligson et al. Nature. 2005. H3K9me2 Prostate, Kidney Seligson et al. Am J Pathol. 2009. Ellinger et al. Prostate 2010. H3K18ac Lung, Kidney Seligson et al. Am J Pathol. 2009. Ellinger et al. Prostate 2010. H3K27me3 (Pg) Prostate Yu et al. Caner Res. 2007. Pfister ey al. Int J Cancer 2008.
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