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Transcription in the absence of Histone H3.2 and H3K4 Methylation


Hödl, Martina; Basler, Konrad (2012). Transcription in the absence of Histone H3.2 and H3K4 Methylation. Current Biology, 22(23):2253-2257.

Abstract

Histone H3 proteins play fundamental roles in DNA packaging, gene transcription, and the transmission of epigenetic states. In addition to posttranslational modifications of their N termini, the use of H3 variants contributes to their regulatory repertoire. Canonical histone H3.2 is expressed during S phase and differs by four amino acid residues from the variant histone H3.3, which is synthesized in a cell-cycle-independent manner [1]. Because H3.3 is enriched within actively transcribed loci [1-3], and because di- and trimethylation of H3 lysine 4 are hallmarks of chromatin at such sites in the genome [4], the H3.3K4 residue is considered to serve as the major regulatory determinant for the transcriptional state of a gene. Here we use genetic approaches in Drosophila to replace all 46 gene copies of His3.2 with mutant derivatives and thereby demonstrate that canonical and variant H3 can functionally replace each other. Cells are able to divide and differentiate when H3.2 is entirely absent but replaced by S phase-expressed H3.3. Moreover, although slowed down in their proliferative capacity, cells that code for a nonmethylatable residue instead of K4 in all canonical and variant H3 genes are competent to respond to major developmental signaling pathways by activating target gene expression. Hence, the presence of different H3 protein species is not essential in Drosophila and transcriptional regulation can occur in the complete absence of H3K4 methylation.

Abstract

Histone H3 proteins play fundamental roles in DNA packaging, gene transcription, and the transmission of epigenetic states. In addition to posttranslational modifications of their N termini, the use of H3 variants contributes to their regulatory repertoire. Canonical histone H3.2 is expressed during S phase and differs by four amino acid residues from the variant histone H3.3, which is synthesized in a cell-cycle-independent manner [1]. Because H3.3 is enriched within actively transcribed loci [1-3], and because di- and trimethylation of H3 lysine 4 are hallmarks of chromatin at such sites in the genome [4], the H3.3K4 residue is considered to serve as the major regulatory determinant for the transcriptional state of a gene. Here we use genetic approaches in Drosophila to replace all 46 gene copies of His3.2 with mutant derivatives and thereby demonstrate that canonical and variant H3 can functionally replace each other. Cells are able to divide and differentiate when H3.2 is entirely absent but replaced by S phase-expressed H3.3. Moreover, although slowed down in their proliferative capacity, cells that code for a nonmethylatable residue instead of K4 in all canonical and variant H3 genes are competent to respond to major developmental signaling pathways by activating target gene expression. Hence, the presence of different H3 protein species is not essential in Drosophila and transcriptional regulation can occur in the complete absence of H3K4 methylation.

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Additional indexing

Item Type:Journal Article, refereed, original work
Communities & Collections:07 Faculty of Science > Institute of Molecular Life Sciences
Dewey Decimal Classification:570 Life sciences; biology
Language:English
Date:4 December 2012
Deposited On:07 Jan 2013 13:38
Last Modified:17 Feb 2018 00:21
Publisher:Cell Press
ISSN:0960-9822
OA Status:Closed
Free access at:Publisher DOI. An embargo period may apply.
Publisher DOI:https://doi.org/10.1016/j.cub.2012.10.008
PubMed ID:23142044

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