Acetyl‐CoA synthases are essential for maintaining histone acetylation under metabolic stress during zygotic genome activation in pigs

ACSS1/2 converts acetate into acetyl‐coenzyme A, which contributes to histone acetylation in the mitochondria and cytoplasm. Zygotic genome activation (ZGA) is critical for embryo development involving drastic histone modification. An efficient crRNAs‐Cas13a targeting strategy was employed to invest...

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Bibliographic Details
Published in:Journal of cellular physiology 2021-10, Vol.236 (10), p.6948-6962
Main Authors: Zhou, Wenjun, Nie, Zheng‐Wen, Zhou, Dong‐Jie, Cui, Xiang‐Shun
Format: Article
Language:English
Subjects:
Acetic acid
Acetylation
ACSS1
ACSS2
Coenzyme A
Cytoplasm
embryo development
Embryos
Fatty acids
Genomes
histone acetylation
Histones
Metabolism
Mitochondria
Nuclear transport
Oxidation
porcine
Pyruvic acid
SIRT1 protein
Swine
Translocation
ZGA
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Summary:ACSS1/2 converts acetate into acetyl‐coenzyme A, which contributes to histone acetylation in the mitochondria and cytoplasm. Zygotic genome activation (ZGA) is critical for embryo development involving drastic histone modification. An efficient crRNAs‐Cas13a targeting strategy was employed to investigate the ACSS1/2 function during ZGA. The results showed that nuclear accumulation of ACSS1 and ACSS2 occurs during ZGA. Knockdown of ACSS1/2 did not affect blastocyst formation when using a normal medium. On culturing embryos in a medium with acetate and no pyruvate (−P + Ace), knockdown of ACSS1 did not affect histone acetylation levels but significantly reduced ATP levels, whereas knockdown of ACSS2 significantly reduced histone acetylation levels in porcine embryos. Inhibition of fatty acid beta‐oxidation by etomoxir significantly reduced ATP levels, which could be restored by acetate. The histone acetylation levels in the ACSS1 and ACSS2 knockdown groups both decreased considerably after etomoxir treatment. Moreover, acetate showed dose‐dependent effects on SIRT1 and SIRT3 levels when under metabolic stress. The C‐terminus of ACSS1 regulated the nuclear translocation. In conclusion, ACSS1/2 helps to maintain ATP and histone acetylation levels in porcine early embryos under metabolic stress during ZGA. New roles of acetyl‐CoA synthases have been implicated in early embryo development. ACSS1 and ACSS2 restore the histone acetylation level and promote early embryo development when under metabolic stress.
ISSN:0021-9541
1097-4652
DOI:10.1002/jcp.30355