Super-enhancer Switching Drives a Burst in Gene Expression at the Mitosis-to-meiosis Transition

Overview

Journal Nat Struct Mol Biol

Specialties Cell Biology
Molecular Biology

Date 2020 Sep 8

PMID 32895557

Citations 30

Authors

So Maezawa

Akihiko Sakashita

Masashi Yukawa

Xiaoting Chen

Kazuki Takahashi

Kris G Alavattam

Ippo Nakata

Matthew T Weirauch

Artem Barski

Satoshi H Namekawa

Affiliations

Soon will be listed here.

Abstract

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.

Citing Articles

CTCF-mediated 3D chromatin sets up the gene expression program in the male germline.

Kitamura Y, Takahashi K, Maezawa S, Munakata Y, Sakashita A, Katz S Nat Struct Mol Biol. 2025; .

PMID: 40033153 DOI: 10.1038/s41594-025-01482-z.

ZBTB16/PLZF regulates juvenile spermatogonial stem cell development through an extensive transcription factor poising network.

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PMID: 40033150 DOI: 10.1038/s41594-025-01509-5.

SETD1B-mediated broad H3K4me3 controls proper temporal patterns of gene expression critical for spermatid development.

Lin Z, Rong B, Lyu R, Zheng Y, Chen Y, Yan J Cell Res. 2025; .

PMID: 40033033 DOI: 10.1038/s41422-025-01080-0.

Site-specific DNA demethylation during spermatogenesis presets the sites of nucleosome retention in mouse sperm.

Maezawa S, Yukawa M, Sakashita A, Barski A, Namekawa S bioRxiv. 2025; .

PMID: 39829778 PMC: 11741358. DOI: 10.1101/2025.01.10.632457.

The conserved genetic program of male germ cells uncovers ancient regulators of human spermatogenesis.

Brattig-Correia R, Almeida J, Wyrwoll M, Julca I, Sobral D, Misra C Elife. 2024; 13.

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