Polycomb group protein-mediated histone modifications during cell differentiation

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Date: Feb. 2015
From: Epigenomics(Vol. 7, Issue 1)
Publisher: Future Medicine Ltd.
Document Type: Report
Length: 7,427 words
Lexile Measure: 2140L

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Author(s): Abdul Aziz Khan aff1 , Andrew Jeoungun Lee aff1 , Tae-Young Roh [*] aff1 aff2

Keywords:

cell differentiation; development; homeobox genes; PcG recruitment; Polycomb group proteins

Generally, all cells in an organism have the same genome but the gene expression pattern of each cell type is different depending on the cellular function and physical location within the organism. The eukaryotic DNA is associated with histones and forms nucleosome structure which provides a gene regulation mechanism as well as a structural stability in a nucleus. The nucleosome structure and its higher order architecture, chromatin have an effect on spatial and temporal gene activation and repression during development and differentiation. The chromatin is subject to many molecular changes such as DNA methylation, post-translational modifications of histones, ATP-dependent chromatin remodeling and conformational alterations by association of noncoding RNAs (ncRNAs) and histone variants.

Polycomb group (PcG) proteins were first identified as regulators of the homeotic genes in embryonic development of Drosophila melanogaster [1-3 ]. So far, various roles of PcG proteins have been studied in the regulation of metazoan developmental genes and the maintenance of embryonic stem (ES) cell pluripotency [4-8 ]. The PRC-mediated repressive patterns on specific genes disappear upon cell differentiation signal through displacement of PcG proteins and removal of H3K27me3 [9 ]. The functional roles of PcG proteins are well elucidated in the regulation of Hox gene clusters during cell differentiation and early development. Defects in the PcG proteins affect the Hox gene expression and ultimately disturb the cell proliferation by chromatin condensation, genomic instability and/or mitotic dysregulation [10 ].

In undifferentiated cells, the expression level of the PcG proteins is broadly high to regulate the developmental stages and make a decision on cell fates. For example, the PcG proteins play a vital role in setting up the lineage commitment during cell differentiation and allowing the development specific genes to timely express [11 ]. The PRC2 components are actively transcribed in retinal progenitor cells of Xenopus and their transcription decreases significantly upon differentiation [ 12 ].

In this review, we discuss about the formation and recruitment of PcG protein complexes and the functional role of PcG proteins focused on the homeotic gene regulation during the early development and cell differentiation.

Formation of polycomb repressive complexes

PcG proteins form dynamic multimeric complexes that selectively control the target genes through histone modifications. Two distinct polycomb complexes, PRC1 and PRC2, are known to be conserved throughout multicellular organisms.

Major components of the PRC1 are RING1A, RING1B and BMI1. The Ring-domain proteins, RING1A and BMI1, possess histone H2A ubiquitin (H2Aub) E3 ligase activities and are involved in maintaining the silencing state of Hox genes and the pluripotency of the ES cells by repressing genes related with differentiation [13,14 ]. In a mouse genetic study, the absence of RING1A shows anterior transformations and unusual axial skeleton patterning [15 ]. RING1B is structurally similar to RING1A and also functions as an E3 ubiquitin ligase, is known to regulate the cell cycle and differentiation-related pathways [7 ]. RING1A/B-mediated silencing is linked...

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Gale Document Number: GALE|A409374834