Pericentromeric heterochromatin is hierarchically organized and spatially contacts H3K9me2 islands in euchromatin.

Abstract

Membraneless pericentromeric heterochromatin (PCH) domains play vital roles in chromosome dynamics and genome stability. However, our current understanding of 3D genome organization does not include PCH domains because of technical challenges associated with repetitive sequences enriched in PCH genomic regions. We investigated the 3D architecture of Drosophila melanogaster PCH domains and their spatial associations with the euchromatic genome by developing a novel analysis method that incorporates genome-wide Hi-C reads originating from PCH DNA. Combined with cytogenetic analysis, we reveal a hierarchical organization of the PCH domains into distinct "territories." Strikingly, H3K9me2-enriched regions embedded in the euchromatic genome show prevalent 3D interactions with the PCH domain. These spatial contacts require H3K9me2 enrichment, are likely mediated by liquid-liquid phase separation, and may influence organismal fitness. Our findings have important implications for how PCH architecture influences the function and evolution of both repetitive heterochromatin and the gene-rich euchromatin.

• Authors: Yuh Chwen G Lee, Yuki Ogiyama, Nuno M C Martins, Brian J Beliveau, David Acevedo, C-Ting Wu, Giacomo Cavalli, Gary H Karpen
• Journal: PLoS genetics (PLoS Genet) Vol. 16 Issue 3 Pg. e1008673 (03 2020) ISSN: 1553-7404 [Electronic] United States
• PMID: 32203508 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• Drosophila Proteins
• Euchromatin
• Heterochromatin
• Histones

Topics

• Animals
• Centrosome (metabolism)
• Chromosome Structures (metabolism)
• Drosophila Proteins (genetics)
• Drosophila melanogaster (genetics)
• Euchromatin (genetics, metabolism)
• Genome (genetics)
• Heterochromatin (genetics, metabolism, ultrastructure)
• Histones (genetics)
• Repetitive Sequences, Nucleic Acid (genetics)