Fig. 7

Interplay of pericentromeric genome organization and epigenetic landscape regulates heterochromatic gene expression. a Distinct genome organization within the pericentromeres partitions the centromeric mega-domains into active and repressed Het TADs which correlate to the expression state of the encompassed heterochromatic genes. TAD borders are enriched for architectural proteins shown in yellow and blue shapes. b RNAi-mediated knockdown of heterochromatic proteins like HP1a or Su(var)3-9, the global TAD structure is largely perturbed but the local intra-TAD interactions are maintained. RNAi of HP1a or Su(var)3-9 minimally affects heterochromatic gene expression. c Drosophila melanogaster active heterochromatic genes, as the name suggests, show enrichment of repressive (H3K9me3/HP1a) and active epigenetic marks like H3K36me3. dADD1, an interactor of HP1a and H3K9me3, binds to upstream of the TSS and is probably involved in the regulation of heterochromatic gene expression in concert with heterochromatic factors (H3K9me3 marks and/or HP1a). dMES-4 (H3K36 methyltransferase) enriched at the pericentromeres is plausibly responsible for the deposition of H3K36me3 marks on the gene bodies of active heterochromatic genes. Mechanistic details of regulation of heterochromatic gene expression by these factors—HP1a, Su(var)3-9, dADD1 and dMES-4 is not well understood. The combinatorial histone mark of H3K9me3/HP1a and H3K36me3 at the exons is likely to regulate the expression of heterochromatic genes differentially from the surrounding repressive heterochromatin, marked by only repressive chromatin signatures