TY - JOUR
T1 - Dynamic reorganization of the genome shapes the recombination landscape in meiotic prophase
AU - Patel, Lucas
AU - Kang, Rhea
AU - Rosenberg, Scott C.
AU - Qiu, Yunjiang
AU - Raviram, Ramya
AU - Chee, Sora
AU - Hu, Rong
AU - Ren, Bing
AU - Cole, Francesca
AU - Corbett, Kevin D.
N1 - Funding Information:
We thank M. Handel for the kind gift of H1T antibodies, members of the Corbett, Cole and Ren labs, and A. Desai for helpful discussions. We thank S. Aigner, M. Neale, G. Fudenberg and L. Mirny for helpful suggestions on Hi-C data interpretation, and M. Griswold and C. Hogarth for assistance with synchronization of spermatogenesis. K.D.C. acknowledges support from the National Institutes of Health (grant No. R01GM104141). F.C. acknowledges support from the National Institutes of Health (grant No. DP2HD087943). K.D.C. and B.R. acknowledge support from the Ludwig Institute for Cancer Research. We acknowledge the National Institutes of Health (grant No. CA16672) for support of the Research Animal Support Facility Smithville, and the CPRIT (grant No. RP170628) for support of the Flow Cytometry and Cellular Imaging Core. R.K. is supported by a CPRIT Research Training Award (No. RP170067). R.R. was supported by a Ruth L. Kirschstein National Research Service Award (no. NIH/NCI T32 CA009523).
Publisher Copyright:
© 2019, The Author(s), under exclusive licence to Springer Nature America, Inc.
PY - 2019/3/1
Y1 - 2019/3/1
N2 - 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.
AB - 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.
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U2 - 10.1038/s41594-019-0187-0
DO - 10.1038/s41594-019-0187-0
M3 - Article
C2 - 30778236
AN - SCOPUS:85061698892
SN - 1545-9993
VL - 26
SP - 164
EP - 174
JO - Nature Structural and Molecular Biology
JF - Nature Structural and Molecular Biology
IS - 3
ER -