H2B ubiquitylation and the histone chaperone Asf1 cooperatively mediate the formation and maintenance of heterochromatin silencing

Nucleic Acids Research
Meng-Ying WuCheng-Fu Kao

Abstract

Heterochromatin is a heritable form of gene repression, with critical roles in development and cell identity. Understanding how chromatin factors results in such repression is a fundamental question. Chromatin is assembled and disassembled during transcription, replication and repair by anti-silencing function 1 (Asf1), a highly conserved histone chaperone. Transcription and DNA replication are also affected by histone modifications that modify nucleosome dynamics, such as H2B ubiquitylation (H2Bub). We report here that H2Bub and Asf1 cooperatively promote transcriptional silencing at yeast telomeres and mating loci. Through real time monitoring of HML (Hidden MAT Left) locus silencing, we found that transcriptional repression was slowly initiated and never fully established in mutants lacking both Asf1 and H2Bub. These findings are consistent with impaired HML silencer-binding and spreading of repressor proteins, Sir2 and Sir3. In addition, mutants lacking H2Bub and Asf1 show defects in both nucleosome assembly and higher-order heterochromatin organization at the HML locus. Our findings reveal a novel role for H2Bub and Asf1 in epigenetic silencing at mating loci. Thus, the interplay between H2Hbub and Asf1 may fine-tune nucle...Continue Reading

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Citations

Feb 22, 2018·Current Genetics·Alexis Zukowski, Aaron M Johnson
Jan 23, 2020·Nucleic Acids Research·Guang YangXiaochun Yu
Nov 9, 2017·Current Genetics·Amparo GalánSusana Rodríguez-Navarro
Dec 31, 2017·The Journal of Biological Chemistry·Alexis ZukowskiAaron M Johnson
May 26, 2021·Trends in Molecular Medicine·Christina Andronikou, Sven Rottenberg

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Methods Mentioned

BETA
acetylation
PCR
chip
chips
flow cytometry
Fluorescence
immunoprecipitation
histone acetylation

Software Mentioned

GeneTraffic
Treeview
GenePix Pro
Cluster
FunSpec
Cyber

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