多梳蛋白群:神经发生中的新兴参与者

Divya Desai, Niloufer P Dumasia, Prasad Pethe
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摘要

神经发育是一个多因素过程,由几个相互关联的因素控制。神经祖细胞的命运是由发育基因、启动子、转录因子和作为转录激活因子或沉默因子的表观遗传修饰因子之间复杂的相互作用决定的。信号分子如- SONIC HEDGEHOG、视黄酸、BMP4、WNT和NOGGIN在发育和分化过程中产生梯度,这些信号分子与其同源受体结合,导致分化所需的特定基因的激活或抑制。非谱系特异性基因的沉默是维持细胞在随后的原肠胚形成后增殖和成熟过程中的身份的关键因素。基因沉默或基因抑制可以通过核苷酸修饰(胞嘧啶甲基化)、组蛋白修饰(乙酰化、甲基化、磷酸化和泛素化)和/或异色化来实现。组蛋白修饰因子如Polycomb Group protein (PcGs)、Histone Acetyltransferases (HAT)、Histone Deacetylases (HDAC)等在发育早期调控基因表达,并在成体生物中发挥重要作用。Polycomb Group蛋白(PcGs)通过催化组蛋白修饰,如组蛋白H3 (H3K27me2和H3K27me3)的二甲基化和三甲基化以及组蛋白H2A (H2AK119Ub)在特定基因启动子上的单泛素化,从而实现基因抑制。本文将讨论Polycomb group (PcG)蛋白在神经发生中的活性,以及它们在组蛋白修饰和关键发育基因沉默中的作用,以实现精确的发育和分化。
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Polycomb group proteins: Emerging players in neurogenesis
Neural development is a multi-factorial process, one that is governed by several interconnected factors. Fate of neural progenitor cells is determined by an intricate interplay between developmental genes, promoters, transcription factors, and epigenetic modifiers that act as transcription activators or silencers. Gradients of signalling molecules such as - SONIC HEDGEHOG, Retinoic Acid, BMP4, WNT and NOGGIN are generated during development and differentiat on, these bind to their cognate receptors leading to activation or repression of specific genes necessary for differentiation. Silencing of nonlineage sp cific genes is a key factor in maintaining the identity of a cell during subsequent proliferation and maturation post gastrulation. Gene silencing or repression of genes can be carried out by nucleotide modifications (cytosine methylation), histone modifications (acetylation, methylation, phosphorylation and ubiquitylation) and/or heterochromatization. Histone modifiers such as Polycomb Group proteins (PcGs), Histone Acetyltransferases (HAT), Histone Deacetylases (HDAC) regulate gene expression in early development as well as play an important role in adult organism. Polycomb Group proteins (PcGs) bring aboutgene repression by catalysing histone modifications such as di- and trimethylation on histone H3 (H3K27me2 and H3K27me3) and mono-ubiquitylation of histone H2A (H2AK119Ub) at the promoters of specific genes. In this review, we would discuss the activity of Polycomb group (PcG) proteins in neurogenesis, their role in histone modification and silencing of key development genes to bring about precise development and differentiation.
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