Histone H2B ubiquitination and beyond: Regulation of nucleosome stability, chromatin dynamics and the trans-histone H3 methylation.
Regulation of Set1-COMPASS-mediated H3K4 methylation and Dot1-mediated H3K79 methylation by H2BK123 ubiquitination (H2Bub1) is an evolutionarily conserved trans-histone crosstalk mechanism. How H2Bub1 impacts chromatin structure and affects Set1-COMPASS/Dot1 functions has not been fully defined. Ubiquitin was proposed to bind proteins to physically bridge H2Bub1 with Set1-COMPASS/Dot1. Alternatively, the bulky ubiquitin was thought to be a "wedge" that loosens the nucleosome for factor access. Contrary to the latter possibility, recent discoveries provide evidence for nucleosome stabilization by H2Bub1 via preventing the constant H2A-H2B eviction. Recent data has also uncovered a "docking-site" on H2B for Set1-COMPASS. Collectively, these findings invoke a model, where ubiquitin acts as a "glue" to bind the nucleosome together for supporting Set1-COMPASS/Dot1 functions. This review provides an overview of these novel findings. Additionally, how H2Bub1 and its deubiquitination might alter the chromatin dynamics during transcription is discussed. Possible models for nucleosome stabilization by ubiquitin are also provided.
Department of Biochemistry and Vanderbilt-Ingram Cancer Center, Vanderbilt University School of Medicine, Nashville, TN, USA.
Mahesh B
MB
Chandrasekharan
Fu
F
Huang
Zu-Wen
ZW
Sun
D042002:Chromatin Assembly and Disassembly / Q000502:physiology*; D042822:Genomic Instability / Q000502:physiology; D000076983:Histone Methyltransferases; D011495:Histone-Lysine N-Methyltransferase / Q000378:metabolism; D006657:Histones / Q000378:metabolism* / Q000502:physiology*; D006801:Humans; D008745:Methylation; D008954:Models, Biological; D008958:Models, Molecular; D009707:Nucleosomes / Q000378:metabolism* / Q000502:physiology; D011499:Protein Processing, Post-Translational; D054875:Ubiquitination / Q000502:physiology*
D006657:Histones; D009707:Nucleosomes; D000076983:Histone Methyltransferases; D011495:Histone-Lysine N-Methyltransferase