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bioRxiv · 10.1101/2023.12.18.572196

Anp32e protects against accumulation of H2A.Z at Sox motif containing promoters during zebrafish gastrulation

Halblander, F. H.·Meng, F. W.·Murphy, P. J.
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Abstract

Epigenetic regulation of chromatin states is crucial for proper gene expression programs and progression during development, but precise mechanisms by which epigenetic factors influence differentiation remain poorly understood. Here we find that the histone variant H2A.Z accumulates at Sox motif-containing promoters during zebrafish gastrulation while neighboring genes become transcriptionally active. These changes coincide with reduced expression of anp32e, the H2A.Z histone removal chaperone, suggesting that loss of Anp32e may lead to increases in H2A.Z during differentiation. Remarkably, genetic removal of Anp32e in embryos leads to H2A.Z accumulation prior to gastrulation, and precocious developmental transcription of Sox motif associated genes. Altogether, our results provide compelling evidence for a mechanism in which Anp32e restricts H2A.Z accumulation at Sox motif-containing promoters, and subsequent down-regulation of Anp32e enables temporal up-regulation of Sox motif associated genes. HighlightsO_LIAn early-developmental time course of zebrafish chromatin accessibility is achieved using an integrated UMAP analysis of datasets from two separate published studies. C_LIO_LICUT&Tag sequencing is used to characterize the genomic localization for the histone chaperone ANP32E. C_LIO_LIChanges in Anp32e enrichment coincide with opposing changes in H2A.Z enrichment during zebrafish gastrulation. C_LIO_LIPrecociously expressed genes in embryos lacking Anp32e are disproportionately Sox-marked and may represent H2A.Z-mediated developmental accelerations. C_LI

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Halblander, F. H., Meng, F. W., Murphy, P. J.. 2023-12-18. Anp32e protects against accumulation of H2A.Z at Sox motif containing promoters during zebrafish gastrulation. https://doi.org/10.1101/2023.12.18.572196

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