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

Autoři: Yuh Chwen G. Lee aff001;  Yuki Ogiyama aff002;  Nuno M. C. Martins aff003;  Brian J. Beliveau aff004;  David Acevedo aff001;  C.-ting Wu aff003;  Giacomo Cavalli aff002;  Gary H. Karpen aff001
Působiště autorů: Department of Molecular and Cell Biology, UC Berkeley and BSE Division, Lawrence Berkeley National Laboratory, Berkeley, California, United States of America aff001;  Institute of Human Genetics, CNRS, Montpellier, France aff002;  Department of Genetics, Blavatnik Institute, Harvard Medical School, Boston, Massachusetts, United States of America aff003;  Department of Genome Sciences, University of Washington, Seattle, Washington, United States of America aff004
Vyšlo v časopise: Pericentromeric heterochromatin is hierarchically organized and spatially contacts H3K9me2 islands in euchromatin. PLoS Genet 16(3): e32767. doi:10.1371/journal.pgen.1008673
Kategorie: Research Article
doi: 10.1371/journal.pgen.1008673


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.

Klíčová slova:

Drosophila melanogaster – Embryos – Fluorescent in situ hybridization – Heterochromatin – Chromosome pairs – Invertebrate genomics – Islands – Euchromatin


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