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Nat Struct Mol Biol. 2019 Mar;26(3):164-174. doi: 10.1038/s41594-019-0187-0. Epub 2019 Feb 18.

Dynamic reorganization of the genome shapes the recombination landscape in meiotic prophase.

Patel L1, Kang R2,3, Rosenberg SC4,5,6, Qiu Y7, Raviram R4, Chee S4, Hu R4, Ren B4,8, Cole F9,10, Corbett KD11,12,13.

Author information

1
Department of Biology, University of California San Diego, La Jolla, CA, USA.
2
Department of Epigenetics and Molecular Carcinogenesis, The University of Texas MD Anderson Cancer Center, Smithville, TX, USA.
3
Genetics and Epigenetics Graduate Program, MD Anderson Cancer Center, UTHealth Graduate School of Biomedical Sciences, Houston, TX, USA.
4
Ludwig Institute for Cancer Research, San Diego Branch, La Jolla, CA, USA.
5
Department of Chemistry and Biochemistry, University of California San Diego, La Jolla, CA, USA.
6
Genentech, South San Francisco, CA, USA.
7
Bioinformatics and Systems Biology Graduate Program, University of California San Diego, La Jolla, CA, USA.
8
Department of Cellular & Molecular Medicine, University of California San Diego, La Jolla, CA, USA.
9
Department of Epigenetics and Molecular Carcinogenesis, The University of Texas MD Anderson Cancer Center, Smithville, TX, USA. fcole@mdanderson.org.
10
Genetics and Epigenetics Graduate Program, MD Anderson Cancer Center, UTHealth Graduate School of Biomedical Sciences, Houston, TX, USA. fcole@mdanderson.org.
11
Ludwig Institute for Cancer Research, San Diego Branch, La Jolla, CA, USA. kcorbett@ucsd.edu.
12
Department of Chemistry and Biochemistry, University of California San Diego, La Jolla, CA, USA. kcorbett@ucsd.edu.
13
Department of Cellular & Molecular Medicine, University of California San Diego, La Jolla, CA, USA. kcorbett@ucsd.edu.

Abstract

In meiotic prophase, chromosomes are organized into compacted loop arrays to promote homolog pairing and recombination. Here, we probe the architecture of the mouse spermatocyte genome in early and late meiotic prophase using chromosome conformation capture (Hi-C). Our data support the established loop array model of meiotic chromosomes, and infer loops averaging 0.8-1.0 megabase pairs (Mb) in early prophase and extending to 1.5-2.0 Mb in late prophase as chromosomes compact and homologs undergo synapsis. Topologically associating domains (TADs) are lost in meiotic prophase, suggesting that assembly of the meiotic chromosome axis alters the activity of chromosome-associated cohesin complexes. While TADs are lost, physically separated A and B compartments are maintained in meiotic prophase. Moreover, meiotic DNA breaks and interhomolog crossovers preferentially form in the gene-dense A compartment, revealing a role for chromatin organization in meiotic recombination. Finally, direct detection of interhomolog contacts genome-wide reveals the structural basis for homolog alignment and juxtaposition by the synaptonemal complex.

PMID:
30778236
PMCID:
PMC6403010
[Available on 2019-08-18]
DOI:
10.1038/s41594-019-0187-0

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