4.6 Article

IGSF11 is required for pericentric heterochromatin dissociation during meiotic diplotene

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PLOS GENETICS
卷 17, 期 9, 页码 -

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PUBLIC LIBRARY SCIENCE
DOI: 10.1371/journal.pgen.1009778

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  1. Ministry of Science and Technology of China

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Deficiency in the adhesion molecule IGSF11, expressed in both somatic cells and germ cells, leads to male infertility in mice, highlighting its importance in meiosis progression. IGSF11 is required for pericentric heterochromatin dissociation in both somatic and germ cells during diplotene in mouse primary spermatocytes.
Meiosis initiation and progression are regulated by both germ cells and gonadal somatic cells. However, little is known about what genes or proteins connecting somatic and germ cells are required for this regulation. Our results show that deficiency for adhesion molecule IGSF11, which is expressed in both Sertoli cells and germ cells, leads to male infertility in mice. Combining a new meiotic fluorescent reporter system with testicular cell transplantation, we demonstrated that IGSF11 is required in both somatic cells and spermatogenic cells for primary spermatocyte development. In the absence of IGSF11, spermatocytes proceed through pachytene, but the pericentric heterochromatin of nonhomologous chromosomes remains inappropriately clustered from late pachytene onward, resulting in undissolved interchromosomal interactions. Hi-C analysis reveals elevated levels of interchromosomal interactions occurring mostly at the chromosome ends. Collectively, our data elucidates that IGSF11 in somatic cells and germ cells is required for pericentric heterochromatin dissociation during diplotene in mouse primary spermatocytes. Author summary For sexually reproducing species, the number of chromosomes in a mature germ cell is half that of a typical somatic cell, and its chromosome sequence is not identical to that of parental cell, these changes result from a highly specialized cell division process named meiosis. In contrast to mitosis, germ cells undergo many meiotic-specific regulatory processes during prophase I of meiosis. In mammals, the development of male and female meiotic germ cells relies on completely different microenvironment provided by sexually specialized gonadal somatic cells, but what gene is required for germ cells and gonadal somatic cells to mediate meiosis progression is largely unclear. Here, we construct a fluorescent reporter to trace meiotic prophase in mice, and use it to examine the requirement of IGSF11 in mediating pericentric heterochromatin dissociation during meiosis.

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