MOF-mediated histone H4 lysine 16 acetylation governs mitochondrial and ciliary functions by controlling promoter interactions (RNA-Seq)

Histone H4 lysine 16 acetylation (H4K16Ac), governed by the histone acetyltransferase (HAT) MOF, orchestrates critical functions in gene expression regulation and chromatin interaction. In this study, we show that conditional genetic deletion of Mof but not Kansl1, the essential component of the NSL complex, causes severe defects during murine skin development. Single-cell and bulk RNA-seq, in combination with MOF ChIP-seq, reveal that numerous MOF targeted and downregulated genes are highly enriched in mitochondria and cilia. Genetic deletion of Uqcrq, an essential subunit for electron transport chain Complex III, recapitulates the defects observed in MOF cKO. Single-cell ATAC-seq reveals that MOF targeted genes are controlled prominently through promoter interactions. Poly(A) enriched whole transcriptome RNAseq on epithelial cells isolated from E16.5 control and MOF/K14Cre cKO mice or P0.5 control and Kansl1/K14Cre cKO mice.