Reorganized 3D Genome Structures Support Transcriptional Regulation in Mouse Spermatogenesis
Zhengyu Luo,
Xiaorong Wang,
Hong Jiang,
Ruoyu Wang,
Jian Chen,
Yusheng Chen,
Qianlan Xu,
Jun Cao,
Xiaowen Gong,
Ji Wu,
Yungui Yang,
Wenbo Li,
Chunsheng Han,
C. Yan Cheng,
Michael G. Rosenfeld,
Fei Sun,
Xiaoyuan Song
Affiliations
Zhengyu Luo
Hefei National Laboratory for Physical Sciences at the Microscale, CAS Key Laboratory of Brain Function and Disease, School of Life Sciences, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, Anhui 230026, China
Xiaorong Wang
Institute of Reproductive Medicine, School of Medicine, Nantong University, Nantong, Jiangsu 226000, China
Hong Jiang
Hefei National Laboratory for Physical Sciences at the Microscale, CAS Key Laboratory of Brain Function and Disease, School of Life Sciences, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, Anhui 230026, China
Ruoyu Wang
Hefei National Laboratory for Physical Sciences at the Microscale, CAS Key Laboratory of Brain Function and Disease, School of Life Sciences, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, Anhui 230026, China; Department of Biochemistry and Molecular Biology, McGovern Medical School, University of Texas Health Science Center, Houston, TX, USA; Graduate School of Biomedical Sciences, University of Texas MD Anderson Cancer Center and UTHealth, Houston, TX, USA
Jian Chen
State Key Laboratory of Stem Cell and Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, China; University of Chinese Academy of Sciences, Beijing 100049, China
Yusheng Chen
University of Chinese Academy of Sciences, Beijing 100049, China; CAS Key Laboratory of Genomic and Precision Medicine, Collaborative Innovation Center of Genetics and Development, CAS Center for Excellence in Molecular Cell Science, College of Future Technology, Beijing Institute of Genomics, Chinese Academy of Sciences, Beijing 100101, China
Qianlan Xu
Hefei National Laboratory for Physical Sciences at the Microscale, CAS Key Laboratory of Brain Function and Disease, School of Life Sciences, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, Anhui 230026, China
Jun Cao
Hefei National Laboratory for Physical Sciences at the Microscale, CAS Key Laboratory of Brain Function and Disease, School of Life Sciences, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, Anhui 230026, China
Xiaowen Gong
Bio-X Institutes, Shanghai Jiao Tong University, Shanghai 200240, China
Ji Wu
Bio-X Institutes, Shanghai Jiao Tong University, Shanghai 200240, China
Yungui Yang
University of Chinese Academy of Sciences, Beijing 100049, China; CAS Key Laboratory of Genomic and Precision Medicine, Collaborative Innovation Center of Genetics and Development, CAS Center for Excellence in Molecular Cell Science, College of Future Technology, Beijing Institute of Genomics, Chinese Academy of Sciences, Beijing 100101, China
Wenbo Li
Department of Biochemistry and Molecular Biology, McGovern Medical School, University of Texas Health Science Center, Houston, TX, USA; Graduate School of Biomedical Sciences, University of Texas MD Anderson Cancer Center and UTHealth, Houston, TX, USA
Chunsheng Han
State Key Laboratory of Stem Cell and Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, China; University of Chinese Academy of Sciences, Beijing 100049, China
C. Yan Cheng
The Mary M. Wohlford Laboratory for Male Contraceptive Research, Center for Biomedical Research, Population Council, New York, USA
Michael G. Rosenfeld
Howard Hughes Medical Institute, School and Department of Medicine, University of California, San Diego School of Medicine, La Jolla, CA 92093-0651, USA
Fei Sun
Institute of Reproductive Medicine, School of Medicine, Nantong University, Nantong, Jiangsu 226000, China; Corresponding author
Xiaoyuan Song
Hefei National Laboratory for Physical Sciences at the Microscale, CAS Key Laboratory of Brain Function and Disease, School of Life Sciences, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, Anhui 230026, China; Corresponding author
Summary: Three-dimensional chromatin structures undergo dynamic reorganization during mammalian spermatogenesis; however, their impacts on gene regulation remain unclear. Here, we focused on understanding the structure-function regulation of meiotic chromosomes by Hi-C and other omics techniques in mouse spermatogenesis across five stages. Beyond confirming recent reports regarding changes in compartmentalization and reorganization of topologically associating domains (TADs), we further demonstrated that chromatin loops are present prior to and after, but not at, the pachytene stage. By integrating Hi-C and RNA-seq data, we showed that the switching of A/B compartments between spermatogenic stages is tightly associated with meiosis-specific mRNAs and piRNAs expression. Moreover, our ATAC-seq data indicated that chromatin accessibility per se is not responsible for the TAD and loop diminishment at pachytene. Additionally, our ChIP-seq data demonstrated that CTCF and cohesin remain bound at TAD boundary regions throughout meiosis, suggesting that dynamic reorganization of TADs does not require CTCF and cohesin clearance. : Male Reproductive Endocrinology; Genomics; Transcriptomics Subject Areas: Male Reproductive Endocrinology, Genomics, Transcriptomics
