Dynamics of activating and repressive histone modifications in Drosophila neural stem cell lineages and brain tumors

果蝇神经干细胞谱系和脑肿瘤中激活和抑制组蛋白修饰的动力学

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作者:Merve Deniz Abdusselamoglu, Lisa Landskron, Sarah K Bowman, Elif Eroglu, Thomas Burkard, Robert E Kingston, Jürgen A Knoblich

Abstract

During central nervous system development, spatiotemporal gene expression programs mediate specific lineage decisions to generate neuronal and glial cell types from neural stem cells (NSCs). However, little is known about the epigenetic landscape underlying these highly complex developmental events. Here, we perform ChIP-seq on distinct subtypes of Drosophila FACS-purified NSCs and their differentiated progeny to dissect the epigenetic changes accompanying the major lineage decisions in vivo By analyzing active and repressive histone modifications, we show that stem cell identity genes are silenced during differentiation by loss of their activating marks and not via repressive histone modifications. Our analysis also uncovers a new set of genes specifically required for altering lineage patterns in type II neuroblasts (NBs), one of the two main Drosophila NSC identities. Finally, we demonstrate that this subtype specification in NBs, unlike NSC differentiation, requires Polycomb-group-mediated repression.

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