Polycomb group proteins: Emerging players in neurogenesis

Abstract

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.

Keywords

• neural development
• polycomb group proteins
• gene silencing