Gene Regulation mediated by Bivalent Chromatin Domains
Year: 2012
Type: dissertation
Abstract: During recent years technical advances have made it possible to study chromatin modifications \nat high resolution in homogenous cell populations. This thesis will focus on recent developments in the \nfield of polycomb-mediated gene silencing and its associated prototypical chromatin mark Histone 3 \nlysine 27 tri-methylation (H3K27me3). Interestingly, vertebrate stem-cell precursor chromatin contains \nso-called bivalently marked genes which are enriched for both H3K27me3 and the opposing and hence \ngene activating mark H3K4me3. Bivalent domains are mostly located at silent genes involved in \nembryogenesis and development and depend on Polycomb Repressive Complexes 2 (PRC2) and 1 (PRC1) \nto be established and maintenaned. It is hypothesized that bivalency is crucial in either timing or poising \nof gene transcription once required during embryogenesis. \nThis thesis discusses several lines of research supporting these claims. Also an alternative \nhypothesis is brought up for the biological relevance of bivalency at specific genes. PRC2 and PRC1 \ncolocalize at a subgroup of bivalent genes. Both complexes are involved in, seemingly, independent \npathways leading to RNA Pol II (RNAP) stalling, hence preventing transcriptional elongation to \ncommence. It is therefore that I suggest bivalency ensures a doubled effort in gene repression during \ncrucial developmental stages. \nElucidating the function of bivalent domains will help us to understand their role in regulating \nembryogenesis. Surprisingly, Drosophila, like other non-vertebrates, lacks bivalent chromatin domains, \neven though homologous target genes, individual chromatin marks and the necessary machineries \ninvolved are al present. Hence, it remains to be clarified what role bivalent domains have in vertebrate \nembryogenesis and eventually how non-vertebrates manage without them.
Author: E.N. van Schaik
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: green
OpenAlex ID: W198021643