Premium
Misregulation of Polycomb Repressive Complexes by Oncohistones
Author(s) -
Lewis Peter W.
Publication year - 2018
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.2018.32.1_supplement.474.3
Subject(s) - chromatin , histone , biology , histone h3 , histone methylation , genetics , histone code , epigenomics , chromatin remodeling , epigenetics , histone h2a , microbiology and biotechnology , histone methyltransferase , histone modifying enzymes , dna methylation , dna , gene , nucleosome , gene expression
Covalent modifications to DNA and the histone packaging proteins allow chromatin to act as a dynamic signaling platform to regulate genomic DNA access and ultimately establish and maintain cellular phenotypes. Moreover, there is increasing appreciation that chromatin alterations per se, including DNA and histone modifications, are involved in the pathogenesis of cancer. Nowhere is this better supported than with the groundbreaking discoveries of high‐frequency, somatic mutations in histones that are drivers of oncogenesis. These mutations (collectively called ‘oncohistones') cause amino acid substitutions that localize to conserved residues in the N‐terminal tail of histone H3 and all seem to be linked, either directly or indirectly, to disruption of normal levels and distribution of histone H3 lysine 27 methylation and thus transcription regulation. We are currently using a combination of biochemical, chromatin and transcriptomic approaches, along with defined cell lines to understand how histone H3 lead to altered chromatin states that profoundly influence gene expression patterns . I will discuss some of our recent work on how histone mutations perturb cellular differentiation through inhibition of specific chromatin‐modifying enzymes. This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal .