Histone variant H3.3 residue S31 is essential for Xenopus gastrulation regardless of the deposition pathway.

Nature Communications
David SitbonGeneviève Almouzni

Abstract

Vertebrates exhibit specific requirements for replicative H3 and non-replicative H3.3 variants during development. To disentangle whether this involves distinct modes of deposition or unique functions once incorporated into chromatin, we combined studies in Xenopus early development with chromatin assays. Here we investigate the extent to which H3.3 mutated at residues that differ from H3.2 rescue developmental defects caused by H3.3 depletion. Regardless of the deposition pathway, only variants at residue 31-a serine that can become phosphorylated-failed to rescue endogenous H3.3 depletion. Although an alanine substitution fails to rescue H3.3 depletion, a phospho-mimic aspartate residue at position 31 rescues H3.3 function. To explore mechanisms involving H3.3 S31 phosphorylation, we identified factors attracted or repulsed by the presence of aspartate at position 31, along with modifications on neighboring residues. We propose that serine 31-phosphorylated H3.3 acts as a signaling module that stimulates the acetylation of K27, providing a chromatin state permissive to the embryonic development program.

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Citations

Jul 16, 2020·Nature Reviews. Molecular Cell Biology·Sara Martire, Laura A Banaszynski
Jul 21, 2020·Epigenetics : Official Journal of the DNA Methylation Society·Nandini Karthik, Reshma Taneja
Aug 31, 2020·Signal Transduction and Targeted Therapy·Hong Wen, Xiaobing Shi
Jul 24, 2020·Nature·Anja ArmacheSteven Z Josefowicz
Oct 15, 2020·Open Biology·Amanuel Tafessu, Laura A Banaszynski
Mar 2, 2021·Immunological Reviews·Alexia Martínez de Paz, Steven Zvi Josefowicz
Mar 28, 2021·Journal of Cell Science·Paul B Talbert, Steven Henikoff
May 8, 2021·Frontiers in Cell and Developmental Biology·Reuben FranklinSihem Cheloufi
Jun 2, 2021·Biochemical Society Transactions·Michael Uckelmann, Chen Davidovich
Mar 31, 2021·Annual Review of Genomics and Human Genetics·Paul B Talbert, Steven Henikoff

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Methods Mentioned

BETA
immunoprecipitations
Immunoprecipitation
pull-down
pulldowns
pulling down
acetylation
in vitro transcription
electrophoresis
Fusion Tribrid

Software Mentioned

MUSCLE
WebLogo3
Sequest HF
Percolator
Zen blue
myProMS
SPOT
Enrichr
ImageJ

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