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Nat Commun. 2019 Oct 3;10(1):4485. doi: 10.1038/s41467-019-12208-3.

Highly structured homolog pairing reflects functional organization of the Drosophila genome.

Author information

1
Department of Genetics, Harvard Medical School, Boston, MA, 02115, USA.
2
Institute for Medical Engineering and Science, Massachusetts Institute of Technology (MIT), Cambridge, MA, 02139, USA.
3
Department of Genetics, Penn Epigenetics Institute, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, 19104-6145, USA.
4
Gladstone Institutes of Data Science and Biotechnology, San Francisco, CA, 94158, USA.
5
Howard Hughes Medical Institute and Program in Systems Biology, Department of Biochemistry and Molecular Pharmacology, University of Massachusetts Medical School, Worcester, MA, 01605-0103, USA.
6
Illumina, San Diego, CA, USA.
7
Institute for Medical Engineering and Science, Massachusetts Institute of Technology (MIT), Cambridge, MA, 02139, USA. leonid@mit.edu.
8
Department of Physics, Massachusetts Institute of Technology (MIT), Cambridge, MA, 02139, USA. leonid@mit.edu.
9
Department of Genetics, Harvard Medical School, Boston, MA, 02115, USA. twu@genetics.med.harvard.edu.
10
Wyss Institute for Biologically Inspired Engineering, Harvard University, Boston, MA, 02115, USA. twu@genetics.med.harvard.edu.

Abstract

Trans-homolog interactions have been studied extensively in Drosophila, where homologs are paired in somatic cells and transvection is prevalent. Nevertheless, the detailed structure of pairing and its functional impact have not been thoroughly investigated. Accordingly, we generated a diploid cell line from divergent parents and applied haplotype-resolved Hi-C, showing that homologs pair with varying precision genome-wide, in addition to establishing trans-homolog domains and compartments. We also elucidate the structure of pairing with unprecedented detail, observing significant variation across the genome and revealing at least two forms of pairing: tight pairing, spanning contiguous small domains, and loose pairing, consisting of single larger domains. Strikingly, active genomic regions (A-type compartments, active chromatin, expressed genes) correlated with tight pairing, suggesting that pairing has a functional implication genome-wide. Finally, using RNAi and haplotype-resolved Hi-C, we show that disruption of pairing-promoting factors results in global changes in pairing, including the disruption of some interaction peaks.

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