Histone Methyltransferase DOT1L is Essential for Self-renewal of Germline Stem Cells

Overview

Journal Genes Dev

Specialty Molecular Biology

Date 2022 Jun 23

PMID 35738678

Authors

Huijuan Lin

Keren Cheng

Hiroshi Kubota

Yemin Lan

Simone S Riedel

Kazue Kakiuchi

Kotaro Sasaki

Kathrin M Bernt

Marisa S Bartolomei

Mengcheng Luo

P Jeremy Wang

Affiliations

Soon will be listed here.

Abstract

Self-renewal of spermatogonial stem cells is vital to lifelong production of male gametes and thus fertility. However, the underlying mechanisms remain enigmatic. Here, we show that DOT1L, the sole H3K79 methyltransferase, is required for spermatogonial stem cell self-renewal. Mice lacking DOT1L fail to maintain spermatogonial stem cells, characterized by a sequential loss of germ cells from spermatogonia to spermatids and ultimately a Sertoli cell only syndrome. Inhibition of DOT1L reduces the stem cell activity after transplantation. DOT1L promotes expression of the fate-determining HoxC transcription factors in spermatogonial stem cells. Furthermore, H3K79me2 accumulates at and genes. Our findings identify an essential function for DOT1L in adult stem cells and provide an epigenetic paradigm for regulation of spermatogonial stem cells.

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