Reduced histone gene copy number disrupts Drosophila Polycomb function.

Autor:	McPherson JE; Curriculum in Genetics and Molecular Biology, University of North Carolina, Chapel Hill, NC, 27599 USA.; Integrative Program for Biological and Genome Sciences, University of North Carolina, Chapel Hill, NC, 27599, USA., Grossmann LC; Department of Biology, University of North Carolina, Chapel Hill, NC, 27599, USA., Armstrong RL; Curriculum in Genetics and Molecular Biology, University of North Carolina, Chapel Hill, NC, 27599 USA.; Integrative Program for Biological and Genome Sciences, University of North Carolina, Chapel Hill, NC, 27599, USA., Kwon E; Department of Biology, University of North Carolina, Chapel Hill, NC, 27599, USA., Salzler HR; Department of Biology, University of North Carolina, Chapel Hill, NC, 27599, USA.; Integrative Program for Biological and Genome Sciences, University of North Carolina, Chapel Hill, NC, 27599, USA., Matera AG; Curriculum in Genetics and Molecular Biology, University of North Carolina, Chapel Hill, NC, 27599 USA.; Department of Biology, University of North Carolina, Chapel Hill, NC, 27599, USA.; Integrative Program for Biological and Genome Sciences, University of North Carolina, Chapel Hill, NC, 27599, USA.; Department of Genetics, University of North Carolina, Chapel Hill, NC, 27599, USA.; Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, NC, 27599, USA., McKay DJ; Curriculum in Genetics and Molecular Biology, University of North Carolina, Chapel Hill, NC, 27599 USA.; Department of Biology, University of North Carolina, Chapel Hill, NC, 27599, USA.; Integrative Program for Biological and Genome Sciences, University of North Carolina, Chapel Hill, NC, 27599, USA.; Department of Genetics, University of North Carolina, Chapel Hill, NC, 27599, USA., Duronio RJ; Curriculum in Genetics and Molecular Biology, University of North Carolina, Chapel Hill, NC, 27599 USA.; Department of Biology, University of North Carolina, Chapel Hill, NC, 27599, USA.; Integrative Program for Biological and Genome Sciences, University of North Carolina, Chapel Hill, NC, 27599, USA.; Department of Genetics, University of North Carolina, Chapel Hill, NC, 27599, USA.; Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, NC, 27599, USA.
Jazyk:	angličtina
Zdroj:	BioRxiv : the preprint server for biology [bioRxiv] 2023 Mar 28. Date of Electronic Publication: 2023 Mar 28.
DOI:	10.1101/2023.03.28.534544
Abstrakt:	The chromatin of animal cells contains two types of histones: canonical histones that are expressed during S phase of the cell cycle to package the newly replicated genome, and variant histones with specialized functions that are expressed throughout the cell cycle and in non-proliferating cells. Determining whether and how canonical and variant histones cooperate to regulate genome function is integral to understanding how chromatin-based processes affect normal and pathological development. Here, we demonstrate that variant histone H3.3 is essential for Drosophila development only when canonical histone gene copy number is reduced, suggesting that coordination between canonical H3.2 and variant H3.3 expression is necessary to provide sufficient H3 protein for normal genome function. To identify genes that depend upon, or are involved in, this coordinate regulation we screened for heterozygous chromosome 3 deficiencies that impair development of flies bearing reduced H3.2 and H3.3 gene copy number. We identified two regions of chromosome 3 that conferred this phenotype, one of which contains the Polycomb gene, which is necessary for establishing domains of facultative chromatin that repress master regulator genes during development. We further found that reduction in Polycomb dosage decreases viability of animals with no H3.3 gene copies. Moreover, heterozygous Polycomb mutations result in de-repression of the Polycomb target gene Ubx and cause ectopic sex combs when either canonical or variant H3 gene copy number is also reduced. We conclude that Polycomb-mediated facultative heterochromatin function is compromised when canonical and variant H3 gene copy number falls below a critical threshold.
Databáze:	MEDLINE
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