Monoubiquitination of Histone H2B Blocks Eviction of Histone Variant H2A.Z from Inducible Enhancers.
Covalent modifications of histones play a crucial role in the regulation of gene expression. Histone H2B monoubiquitination has mainly been described as a regulator of transcription elongation, but its role in transcription initiation is poorly documented. We investigated the role of this histone mark (H2Bub1) on different inducible enhancers, in particular those regulated by estrogen receptor α, by loss- and gain-of-function experiments with the specific E3-ubiquitin ligase complex of H2B: RNF20/RNF40. RNF20/RNF40 overexpression causes repression of the induced activity of these enhancers. Genome-wide profiles show that H2Bub1 levels are negatively correlated with the accessibility of enhancers to transcriptional activators. We found that the chromatin association of histone variant H2A.Z, which is evicted from enhancers for transcriptional activation, is stabilized by H2Bub1 by impairing access of the chromatin remodeler INO80. We propose that H2Bub1 acts as a gatekeeper of H2A.Z eviction and activation of inducible enhancers.
Département de Biologie Cellulaire, Université de Genève, 1211 Genève 4, Switzerland; Institute of Genetics and Genomics of Geneva, Université de Genève, 1211 Genève 4, Switzerland.
Gregory
G
Segala
Département de Biologie Cellulaire, Université de Genève, 1211 Genève 4, Switzerland; Institute of Genetics and Genomics of Geneva, Université de Genève, 1211 Genève 4, Switzerland.
Marcela A
MA
Bennesch
Département de Biologie Cellulaire, Université de Genève, 1211 Genève 4, Switzerland.
Deo Prakash
DP
Pandey
Institute of Genetics and Genomics of Geneva, Université de Genève, 1211 Genève 4, Switzerland.
Nicolas
N
Hulo
Département de Biologie Cellulaire, Université de Genève, 1211 Genève 4, Switzerland; Institute of Genetics and Genomics of Geneva, Université de Genève, 1211 Genève 4, Switzerland. Electronic address: didier.picard@unige.ch.
Didier
D
Picard
D000074183:ATPases Associated with Diverse Cellular Activities; D045744:Cell Line, Tumor; D002843:Chromatin / Q000737:chemistry* / Q000378:metabolism; D042002:Chromatin Assembly and Disassembly; D004265:DNA Helicases / Q000235:genetics* / Q000378:metabolism; D004268:DNA-Binding Proteins; D004742:Enhancer Elements, Genetic; D004847:Epithelial Cells / Q000166:cytology / Q000378:metabolism; D047628:Estrogen Receptor alpha / Q000235:genetics / Q000378:metabolism; D020869:Gene Expression Profiling; D017930:Genes, Reporter; D057809:HEK293 Cells; D006657:Histones / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D008156:Luciferases / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D015533:Transcriptional Activation; D044767:Ubiquitin-Protein Ligases / Q000235:genetics* / Q000378:metabolism; D054875:Ubiquitination
D002843:Chromatin; D004268:DNA-Binding Proteins; D047628:Estrogen Receptor alpha; D006657:Histones; C077020:histone H2A.F-Z; D008156:Luciferases; C506646:RNF20 protein, human; C413363:RNF40 protein, human; D044767:Ubiquitin-Protein Ligases; D000074183:ATPases Associated with Diverse Cellular Activities; D004265:DNA Helicases; C524421:INO80 protein, human
INO80; breast cancer; chromatin; chromatin remodeling; epigenetics; estrogen receptor; histone; transcription factor; transcription initiation; ubiquitylation