Spt6 is a maintenance factor for centromeric CENP-A.

Nature Communications
Georg O M BobkovPatrick Heun

Abstract

Replication and transcription of genomic DNA requires partial disassembly of nucleosomes to allow progression of polymerases. This presents both an opportunity to remodel the underlying chromatin and a danger of losing epigenetic information. Centromeric transcription is required for stable incorporation of the centromere-specific histone dCENP-A in M/G1 phase, which depends on the eviction of previously deposited H3/H3.3-placeholder nucleosomes. Here we demonstrate that the histone chaperone and transcription elongation factor Spt6 spatially and temporarily coincides with centromeric transcription and prevents the loss of old CENP-A nucleosomes in both Drosophila and human cells. Spt6 binds directly to dCENP-A and dCENP-A mutants carrying phosphomimetic residues alleviate this association. Retention of phosphomimetic dCENP-A mutants is reduced relative to wildtype, while non-phosphorylatable dCENP-A retention is increased and accumulates at the centromere. We conclude that Spt6 acts as a conserved CENP-A maintenance factor that ensures long-term stability of epigenetic centromere identity during transcription-mediated chromatin remodeling.

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Citations

Sep 16, 2020·The Journal of Cell Biology·Sreyoshi MitraLars E T Jansen
Aug 14, 2020·Genes·Ganesan Arunkumar, Daniël P Melters
Nov 23, 2020·Current Genetics·Cinzia KlemmGuðjón Ólafsson
Apr 22, 2021·The Journal of Cell Biology·Yujue ChenHong Liu
May 8, 2021·Frontiers in Cell and Developmental Biology·Reuben FranklinSihem Cheloufi

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Methods Mentioned

BETA
pull-down
histone acetylation
fluorescence microscopy
transgenic
fluorescence-activated cell sorting
co-IPs
co-immunoprecipitation
salt
co-IP
transfection

Key Resources (RRID) Mentioned

Addgene_49330

Software Mentioned

GraphPad Prism
Clustal Omega
ImageJ
Prism
softWoRx Explorer Suite

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