Reduced histone gene copy number disrupts Drosophila Polycomb function.
Reduced histone gene copy number disrupts Drosophila Polycomb function.
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组蛋白基因拷贝数减少会破坏果蝇多梳功能。
DOI：
10.1093/genetics/iyad106
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发表时间：
2023
期刊：
影响因子：
3.3
通讯作者：
Duronio,RobertJ
中科院分区：
文献类型：
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作者：
McPherson,Jeanne-MarieE;Grossmann,LucyC;Salzler,HarmonyR;Armstrong,RobinL;Kwon,Esther;Matera,AGregory;McKay,DanielJ;Duronio,RobertJ
动物细胞的染色质含有两种类型的组蛋白：在细胞周期的S期期间表达以包装新复制的基因组的典型组蛋白，以及在整个细胞周期和非增殖细胞中表达的具有专门功能的变体组蛋白。确定典型组蛋白和变异组蛋白是否以及如何合作调节基因组功能是理解基于染色质的过程如何影响正常和病理发育的组成部分。在这里，我们证明了只有当典型组蛋白基因拷贝数减少时，变异组蛋白H3.3才是果蝇发育所必需的，这表明典型组蛋白H3.2和变异组蛋白H3.3表达之间的协调是必要的，以提供足够的H3蛋白用于正常的基因组功能。为了鉴定依赖于或参与这种协调调节的基因，我们筛选了杂合3号染色体缺陷，这些缺陷损害了携带减少的H3.2和H3.3基因拷贝数的果蝇的发育。我们确定了3号染色体的两个区域，赋予这种表型，其中之一包含的polycomb基因，这是必要的建立兼性染色质抑制主调节基因在发展过程中的结构域。我们进一步发现，Polycomb剂量的减少降低了无H3.3基因拷贝动物的生存力。此外，异源Polycomb突变导致Polycomb靶基因Ubx的去抑制，并且当典型或变体H3基因拷贝数减少时引起异位性梳。我们的结论是，Polycomb介导的兼性异染色质功能受到损害时，典型和variantH3基因拷贝数福尔斯低于临界阈值。
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 forDrosophiladevelopment only when canonical histone gene copy number is reduced, suggesting that coordination between canonicalH3.2and variantH3.3expression 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 reducedH3.2andH3.3gene copy number. We identified two regions of chromosome 3 that conferred this phenotype, one of which contains thePolycombgene, which is necessary for establishing domains of facultative chromatin that repress master regulator genes during development. We further found that reduction inPolycombdosage decreases viability of animals with noH3.3gene copies. Moreover, heterozygousPolycombmutations result in de-repression of the Polycomb target geneUbxand cause ectopic sex combs when either canonical or variantH3gene copy number is reduced. We conclude that Polycomb-mediated facultative heterochromatin function is compromised when canonical and variantH3gene copy number falls below a critical threshold.