Fig. 8: Working model illustration of Echs1-mediated histone crotonylation regulating early embryo development.

Echs1 supports early embryo development by regulating crotonyl-CoA synthesis to generate histone crotonylation. Under physiological condition, Echs1 sustains normal level of crotonyl-CoA in early embryos, ensuring sufficient histone crotonylation for transcription activation at ZGA genes, retrotransposon elements, and rDNA loci, thereby ensuring normal early embryo development. When Echs1 is deficient, histone crotonylation level decreases, ZGA event fails, maternal mRNA degradation is impaired, mitochondrial dysfunction occurs, and embryonic development is arrested. Additionally, the addition of exogenous crotonate to the culture medium of embryos from aged female mice improves blastocyst formation. In summary, Echs1-mediated histone crotonylation is crucial for transcription activation of ZGA genes and repetitive elements to support early embryo development.