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

Lucas Patel, Rhea Kang, Scott C. Rosenberg, Yunjiang Qiu, Ramya Raviram, Sora Chee, Rong Hu, Bing Ren, Francesca Cole, Kevin D. Corbett

Research output: Contribution to journalArticlepeer-review

91 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)164-174
Number of pages11
JournalNature Structural and Molecular Biology
Volume26
Issue number3
DOIs
StatePublished - Mar 1 2019

ASJC Scopus subject areas

  • Structural Biology
  • Molecular Biology

MD Anderson CCSG core facilities

  • Flow Cytometry and Cellular Imaging Facility
  • Research Animal Support Facility
  • Science Park Flow Cytometry

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