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Histone methyltransferase DOT1L is essential for self-renewal of germline stem cells

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 fai...

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Autores principales: Lin, Huijuan, Cheng, Keren, Kubota, Hiroshi, Lan, Yemin, Riedel, Simone S., Kakiuchi, Kazue, Sasaki, Kotaro, Bernt, Kathrin M., Bartolomei, Marisa S., Luo, Mengcheng, Wang, P. Jeremy
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Cold Spring Harbor Laboratory Press 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9296001/
https://www.ncbi.nlm.nih.gov/pubmed/35738678
http://dx.doi.org/10.1101/gad.349550.122
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author Lin, Huijuan
Cheng, Keren
Kubota, Hiroshi
Lan, Yemin
Riedel, Simone S.
Kakiuchi, Kazue
Sasaki, Kotaro
Bernt, Kathrin M.
Bartolomei, Marisa S.
Luo, Mengcheng
Wang, P. Jeremy
author_facet Lin, Huijuan
Cheng, Keren
Kubota, Hiroshi
Lan, Yemin
Riedel, Simone S.
Kakiuchi, Kazue
Sasaki, Kotaro
Bernt, Kathrin M.
Bartolomei, Marisa S.
Luo, Mengcheng
Wang, P. Jeremy
author_sort Lin, Huijuan
collection PubMed
description 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 HoxC9 and HoxC10 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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spelling pubmed-92960012022-12-01 Histone methyltransferase DOT1L is essential for self-renewal of germline stem cells Lin, Huijuan Cheng, Keren Kubota, Hiroshi Lan, Yemin Riedel, Simone S. Kakiuchi, Kazue Sasaki, Kotaro Bernt, Kathrin M. Bartolomei, Marisa S. Luo, Mengcheng Wang, P. Jeremy Genes Dev Research Paper 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 HoxC9 and HoxC10 genes. Our findings identify an essential function for DOT1L in adult stem cells and provide an epigenetic paradigm for regulation of spermatogonial stem cells. Cold Spring Harbor Laboratory Press 2022-06-01 /pmc/articles/PMC9296001/ /pubmed/35738678 http://dx.doi.org/10.1101/gad.349550.122 Text en © 2022 Lin et al.; Published by Cold Spring Harbor Laboratory Press https://creativecommons.org/licenses/by-nc/4.0/This article is distributed exclusively by Cold Spring Harbor Laboratory Press for the first six months after the full-issue publication date (see http://genesdev.cshlp.org/site/misc/terms.xhtml). After six months, it is available under a Creative Commons License (Attribution-NonCommercial 4.0 International), as described at http://creativecommons.org/licenses/by-nc/4.0/ (https://creativecommons.org/licenses/by-nc/4.0/) .
spellingShingle Research Paper
Lin, Huijuan
Cheng, Keren
Kubota, Hiroshi
Lan, Yemin
Riedel, Simone S.
Kakiuchi, Kazue
Sasaki, Kotaro
Bernt, Kathrin M.
Bartolomei, Marisa S.
Luo, Mengcheng
Wang, P. Jeremy
Histone methyltransferase DOT1L is essential for self-renewal of germline stem cells
title Histone methyltransferase DOT1L is essential for self-renewal of germline stem cells
title_full Histone methyltransferase DOT1L is essential for self-renewal of germline stem cells
title_fullStr Histone methyltransferase DOT1L is essential for self-renewal of germline stem cells
title_full_unstemmed Histone methyltransferase DOT1L is essential for self-renewal of germline stem cells
title_short Histone methyltransferase DOT1L is essential for self-renewal of germline stem cells
title_sort histone methyltransferase dot1l is essential for self-renewal of germline stem cells
topic Research Paper
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9296001/
https://www.ncbi.nlm.nih.gov/pubmed/35738678
http://dx.doi.org/10.1101/gad.349550.122
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