Transcription of genes residing within constitutive heterochromatin is paradoxical to the tenets of epigenetic code. The regulatory mechanisms of Drosophila melanogaster heterochromatic gene transcription remain largely unknown. Emerging evidence suggests that genome organization and transcriptional regulation are inter-linked. However, the pericentromeric genome organization is relatively less studied. Therefore, we sought to characterize the pericentromeric genome organization and understand how this organization along with the pericentromeric factors influences heterochromatic gene expression. Here, we characterized the pericentromeric genome organization in Drosophila melanogaster using 5C sequencing. Heterochromatic topologically associating domains (Het TADs) correlate with distinct epigenomic domains of active and repressed heterochromatic genes at the pericentromeres. These genes are known to depend on the heterochromatic landscape for their expression. However, HP1a or Su(var)3-9 RNAi has minimal effects on heterochromatic gene expression, despite causing significant changes in the global Het TAD organization. Probing further into this observation, we report the role of two other chromatin proteins enriched at the pericentromeres-dMES-4 and dADD1 in regulating the expression of a subset of heterochromatic genes. Distinct pericentromeric genome organization and chromatin landscapes maintained by the interplay of heterochromatic factors (HP1a, H3K9me3, dMES-4 and dADD1) are sufficient to support heterochromatic gene expression despite the loss of global Het TAD structure. These findings open new avenues for future investigations into the mechanisms of heterochromatic gene expression.

中文翻译：

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着丝粒基因组组织和染色质景观的相互作用调节果蝇果蝇异色基因的表达

组成型异染色质中基因的转录与表观遗传密码的原理是矛盾的。果蝇黑变色基因转录的调控机制仍然是未知的。新兴证据表明，基因组的组织和转录调控是相互联系的。然而，围绕着着丝粒的基因组组织研究相对较少。因此，我们试图表征着丝粒中心基因组的组织，并了解这种组织以及着丝粒中心因子如何影响异色基因表达。在这里，我们使用5C测序表征了果蝇果腹中的着丝粒基因组组织。异色拓扑关联域（Het TAD）与周围着丝粒处的活跃和受阻异色基因的独特表观基因组域相关。这些基因的表达依赖于异色景观。但是，HP1a或Su（var）3-9 RNAi对异色基因表达的影响很小，尽管在全球Het TAD组织中引起了重大变化。进一步探究这一发现，我们报告了富集在着丝粒-dMES-4和dADD1上的其他两种染色质蛋白在调节异色基因子集表达中的作用。不同的着丝粒基因组组织和染色质景观由异色因子（HP1a，H3K9me3，尽管丢失了完整的Het TAD结构，但dMES-4和dADD1）足以支持异色基因表达。这些发现为今后进一步研究异色基因表达的机制开辟了新途径。