4.8 Article

Three-dimensional genome structure shapes the recombination landscape of chromatin features during female germline stem cell development

Journal

CLINICAL AND TRANSLATIONAL MEDICINE
Volume 12, Issue 6, Pages -

Publisher

JOHN WILEY & SONS LTD
DOI: 10.1002/ctm2.927

Keywords

chromatin structure; FGSC development; Hi-C

Funding

  1. National Key Research and Development Program of China [2017YFA0504201]
  2. National Natural Science Foundation of China [81720108017, 31871329]
  3. China Postdoctoral Science Foundation [2021M692081]
  4. National Major Scientific Instruments and Equipment Development Project, National Nature Science Foundation of China [61827814]

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This study investigated the three-dimensional structure of chromatin during the development of female germline stem cells (FGSCs) using high-throughput chromosome conformation capture technique. The results showed significant reorganization of the global 3D genome during FGSC development, with specific changes observed in the chromatin structure of topologically associating domains. The study also identified conserved chromatin structures between FGSC development and early embryonic development.
Background During meiosis of mammalian cells, chromatin undergoes drastic reorganization. However, the dynamics of the three-dimensional (3D) chromatin structure during the development of female germline stem cells (FGSCs) are poorly understood. Methods The high-throughput chromosome conformation capture technique was used to probe the 3D structure of chromatin in mouse germ cells at each stage of FGSC development. Results The global 3D genome was dramatically reorganized during FGSC development. In topologically associating domains, the chromatin structure was weakened in germinal vesicle stage oocytes and still present in meiosis I stage oocytes but had vanished in meiosis II oocytes. This switch between topologically associating domains was related to the biological process of FGSC development. Moreover, we constructed a landscape of chromosome X organization, which showed that the X chromosome occupied a smaller proportion of the active (A) compartment than the autosome during FGSC development. By comparing the high-order chromatin structure between female and male germline development, we found that 3D genome organization was remodelled by two different potential mechanisms during gamete development, in which interchromosomal interactions, compartments, and topologically associating domain were decreased during FGSC development but reorganized and recovered during spermatogenesis. Finally, we identified conserved chromatin structures between FGSC development and early embryonic development. Conclusions These results provide a valuable resource to characterize chromatin organization and for further studies of FGSC development.

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