德国马克斯普朗克研究所Asifa Akhtar研究组的一项最新研究发现,代际维持的组蛋白H4第16位赖氨酸乙酰化影响子代的基因激活。这一研究成果于2020年6月4日在线发表在《细胞》上。
Title: Intergenerationally Maintained Histone H4 Lysine 16 Acetylation Is Instructive for Future Gene Activation
Author: Maria Samata, Anastasios Alexiadis, Gautier Richard, Plamen Georgiev, Johannes Nuebler, Tanvi Kulkarni, Gina Renschler, M. Felicia Basilicata, Fides Lea Zenk, Maria Shvedunova, Giuseppe Semplicio, Leonid Mirny, Nicola Iovino, Asifa Akhtar
Issue&Volume: 2020-06-04
Abstract: Before zygotic genome activation (ZGA), the quiescent genome undergoes reprogrammingto transition into the transcriptionally active state. However, the mechanisms underlyingeuchromatin establishment during early embryogenesis remain poorly understood. Here,we show that histone H4 lysine 16 acetylation (H4K16ac) is maintained from oocytesto fertilized embryos in Drosophila and mammals. H4K16ac forms large domains that control nucleosome accessibility ofpromoters prior to ZGA in flies. Maternal depletion of MOF acetyltransferase leadingto H4K16ac loss causes aberrant RNA Pol II recruitment, compromises the 3D organizationof the active genomic compartments during ZGA, and causes downregulation of post-zygoticallyexpressed genes. Germline depletion of histone deacetylases revealed that other acetylmarks cannot compensate for H4K16ac loss in the oocyte. Moreover, zygotic re-expressionof MOF was neither able to restore embryonic viability nor onset of X chromosome dosagecompensation. Thus, maternal H4K16ac provides an instructive function to the offspring,priming future gene activation.
DOI: 10.1016/j.cell.2020.05.026
Source: https://www.cell.com/cell/fulltext/S0092-8674(20)30621-8