NatB domain-containing CRA-1 antagonizes hydrolase ACER-1 linking acetyl-CoA metabolism to the initiation of recombination during C. elegans meiosis

PLoS Genetics
Jinmin GaoMonica P Colaiácovo

Abstract

The formation of DNA double-strand breaks (DSBs) must take place during meiosis to ensure the formation of crossovers, which are required for accurate chromosome segregation, therefore avoiding aneuploidy. However, DSB formation must be tightly regulated to maintain genomic integrity. How this regulation operates in the context of different chromatin architectures and accessibility, and how it is linked to metabolic pathways, is not understood. We show here that global histone acetylation levels undergo changes throughout meiotic progression. Moreover, perturbations to global histone acetylation levels are accompanied by changes in the frequency of DSB formation in C. elegans. We provide evidence that the regulation of histone acetylation requires CRA-1, a NatB domain-containing protein homologous to human NAA25, which controls the levels of acetyl-Coenzyme A (acetyl-CoA) by antagonizing ACER-1, a previously unknown and conserved acetyl-CoA hydrolase. CRA-1 is in turn negatively regulated by XND-1, an AT-hook containing protein. We propose that this newly defined protein network links acetyl-CoA metabolism to meiotic DSB formation via modulation of global histone acetylation.

References

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Citations

Dec 10, 2017·Cold Spring Harbor Symposia on Quantitative Biology·Takamune T Saito, Monica P Colaiácovo
Oct 22, 2016·G3 : Genes - Genomes - Genetics·T Brooke McClendonJudith L Yanowitz
Oct 2, 2019·Proceedings of the National Academy of Sciences of the United States of America·Katherine Kretovich BillmyreR Scott Hawley
May 14, 2016·G3 : Genes - Genomes - Genetics·Max R Bernstein, Matthew V Rockman
Jan 2, 2018·Trends in Genetics : TIG·Jinmin Gao, Monica P Colaiácovo
Jun 4, 2021·Journal of Molecular Cell Biology·Yuanyuan LiuJinmin Gao

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Methods Mentioned

BETA
histone acetylation
acetylation
transgenic
ChIP-Seq
Fluoresence
immunoprecipitation
Assay
in vitro transcription

Software Mentioned

Photoshop
ImageJ
Image J
SoftWoRx
HHPRED

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