Functional Redundancy of Variant and Canonical Histone H3 Lysine 9 Modification in Drosophila

Genetics: A Periodical Record of Investigations Bearing on Heredity and Variation

Daniel J. McKay^2¹  Taylor J. R. Penke^1²  Robert J. Duronio^4⁵  A. Gregory Matera^4⁶  Brian D. Strahl^3⁷ 

[1]Curriculum in Genetics and Molecular Biology, The University of North Carolina at Chapel Hill, North Carolina 27599

[2]Curriculum in Genetics and Molecular Biology, The University of North Carolina at Chapel Hill, North Carolina 27599^1

[3]Department of Biochemistry and Biophysics, The University of North Carolina at Chapel Hill, North Carolina 27599

[4]Department of Biology, The University of North Carolina at Chapel Hill, North Carolina 27599

[5]Department of Biology, The University of North Carolina at Chapel Hill, North Carolina 27599^2

[6]Department of Genetics, The University of North Carolina at Chapel Hill, North Carolina 27599

[7]Integrative Program for Biological and Genome Sciences, The University of North Carolina at Chapel Hill, North Carolina 27599

[8]Lineberger Comprehensive Cancer Center, The University of North Carolina at Chapel Hill, North Carolina 27599^3

[9]Lineberger Comprehensive Cancer Center, The University of North Carolina at Chapel Hill, North Carolina 27599^4

关键词: Drosophila;    histone variant;    H3;    transcription;    heterochromatin;   

DOI  :  10.1534/genetics.117.300480

学科分类：医学（综合）

来源: Genetics Society of America

【 摘 要 】

Histone post-translational modifications (PTMs) and differential incorporation of variant and canonical histones into chromatin are central modes of epigenetic regulation. Despite similar protein sequences, histone variants are enriched for different suites of PTMs compared to their canonical counterparts. For example, variant histone H3.3 occurs primarily in transcribed regions and is enriched for “active” histone PTMs like Lys9 acetylation (H3.3K9ac), whereas the canonical histone H3 is enriched for Lys9 methylation (H3K9me), which is found in transcriptionally silent heterochromatin. To determine the functions of K9 modification on variant vs. canonical H3, we compared the phenotypes caused by engineering H3.3^K9R and H3^K9R mutant genotypes in Drosophila melanogaster . Whereas most H3.3^K9R , and a small number of H3^K9R , mutant animals are capable of completing development and do not have substantially altered protein-coding transcriptomes, all H3.3^K9R H3^K9R combined mutants die soon after embryogenesis and display decreased expression of genes enriched for K9ac. These data suggest that the role of K9ac in gene activation during development can be provided by either H3 or H3.3. Conversely, we found that H3.3K9 is methylated at telomeric transposons and that this mark contributes to repressive chromatin architecture, supporting a role for H3.3 in heterochromatin that is distinct from that of H3. Thus, our genetic and molecular analyses demonstrate that K9 modification of variant and canonical H3 have overlapping roles in development and transcriptional regulation, though to differing extents in euchromatin and heterochromatin.

【 授权许可】

CC BY