TY - JOUR
T1 - Super-enhancer switching drives a burst in gene expression at the mitosis-to-meiosis transition
AU - Maezawa, So
AU - Sakashita, Akihiko
AU - Yukawa, Masashi
AU - Chen, Xiaoting
AU - Takahashi, Kazuki
AU - Alavattam, Kris G.
AU - Nakata, Ippo
AU - Weirauch, Matthew T.
AU - Barski, Artem
AU - Namekawa, Satoshi H.
N1 - Funding Information:
We thank members of the Namekawa and Maezawa laboratories for discussions and helpful comments regarding the manuscript. We also thank the CCHMC Research Flow Cytometry Core for sharing MACS equipment, X. Li at the University of Rochester Medical Center for sharing A-myb mutant mice and M.A. Handel at the Jackson Laboratory for sharing the H1T antibody. We acknowledge the following funding sources: a research project grant by the Azabu University Research Services Division, Ministry of Education, Culture, Sports, Science and Technology (MEXT)-Supported Program for the Private University Research Branding Project (2016–2019); a Grant-in-Aid for Research Activity Start-up (19K21196); the Takeda Science Foundation (2019); and the Uehara Memorial Foundation Research Incentive Grant (2018) to S.M.; a Lalor Foundation Postdoctoral Fellowship and JSPS Overseas Research Fellowships to A.S.; an Albert J. Ryan Fellowship to K.G.A.; CCHMC Endowed Scholar and CpG grant awards to M.T.W.; National Institute of Health (NIH) DP2 GM119134 grant to A.B.; and NIH R01 GM122776 and GM098605 grants to S.H.N.
Publisher Copyright:
© 2020, The Author(s), under exclusive licence to Springer Nature America, Inc.
PY - 2020/10/1
Y1 - 2020/10/1
N2 - Owing to bursts in the expression of thousands of germline-specific genes, the testis has the most diverse and complex transcriptome of all organs. By analyzing the male germline of mice, we demonstrate that the genome-wide reorganization of super-enhancers (SEs) drives bursts in germline gene expression after the mitosis-to-meiosis transition. SE reorganization is regulated by two molecular events: the establishment of meiosis-specific SEs via A-MYB (MYBL1), a key transcription factor for germline genes, and the resolution of SEs in mitotically proliferating cells via SCML2, a germline-specific Polycomb protein required for spermatogenesis-specific gene expression. Before entry into meiosis, meiotic SEs are preprogrammed in mitotic spermatogonia to ensure the unidirectional differentiation of spermatogenesis. We identify key regulatory factors for both mitotic and meiotic enhancers, revealing a molecular logic for the concurrent activation of mitotic enhancers and suppression of meiotic enhancers in the somatic and/or mitotic proliferation phases.
AB - Owing to bursts in the expression of thousands of germline-specific genes, the testis has the most diverse and complex transcriptome of all organs. By analyzing the male germline of mice, we demonstrate that the genome-wide reorganization of super-enhancers (SEs) drives bursts in germline gene expression after the mitosis-to-meiosis transition. SE reorganization is regulated by two molecular events: the establishment of meiosis-specific SEs via A-MYB (MYBL1), a key transcription factor for germline genes, and the resolution of SEs in mitotically proliferating cells via SCML2, a germline-specific Polycomb protein required for spermatogenesis-specific gene expression. Before entry into meiosis, meiotic SEs are preprogrammed in mitotic spermatogonia to ensure the unidirectional differentiation of spermatogenesis. We identify key regulatory factors for both mitotic and meiotic enhancers, revealing a molecular logic for the concurrent activation of mitotic enhancers and suppression of meiotic enhancers in the somatic and/or mitotic proliferation phases.
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U2 - 10.1038/s41594-020-0488-3
DO - 10.1038/s41594-020-0488-3
M3 - Article
C2 - 32895557
AN - SCOPUS:85090307017
SN - 1545-9993
VL - 27
SP - 978
EP - 988
JO - Nature Structural and Molecular Biology
JF - Nature Structural and Molecular Biology
IS - 10
ER -