Aging, Environment, & DiseaseChromatin StructureHistone Modifications

Gene Transcription: Not Always Dictated by Histone Modifications!

Gene Transcription: Not Always Dictated by Histone Modifications!The proper regulation of gene expression is of fundamental importance in the maintenance of normal growth and development.  Misregulation of genes can lead to such outcomes as cancer, diabetes and neurodegenerative disease.  A key step in gene regulation occurs during the transcription of the chromosomal DNA into messenger RNA by the enzyme, RNA polymerase II.

Histones are small, positively charged proteins that package genomic DNA into arrays of bead-like particles termed nucleosomes, the principal components of chromatin.  Increasing evidence suggests that nucleosomal histones play an active role in regulating transcription, and that this is derived in part from reversible chemical (“covalent”) modifications that take place on their amino acids.  These histone modifications create novel surfaces on nucleosomes that can serve as docking sites for other proteins that control a gene’s expression state.  In the study by Zhang et al, PLoS Genetics April 2014, the authors show that contrary to the general case, covalent modifications typically associated with transcription are minimally used by genes embedded in a specialized, condensed chromatin structure termed heterochromatin in the model organism baker’s yeast (Saccharomyces cerevisiae). Modifications negligibly utilized include H3K4 trimethylation, H3K36 trimethylation and H3K79 dimethylation, marks commonly linked to transcription initiation and elongation.  Heterochromatic gene activation was also observed to occur with minimal H3 and H4 lysine acetylation, a covalent modification long correlated with gene expression, and without replacement of H2A with the transcription-linked variant H2A.Z.

The observations of the Gross laboratory are significant, for they suggest that gene transcription can occur in a living cell in the virtual absence of covalent modification of the chromatin template.

 

Zhang H, Gao L, Anandhakumar J, & Gross DS (2014). Uncoupling transcription from covalent histone modification. PLoS genetics, 10 (4) PMID: 24722509

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