SETDB1 is essential for mouse primordial germ cell fate determination by ensuring BMP signaling [RESEARCH ARTICLE]

Publication Date:
2018-12-11
Publisher:
The Company of Biologists
Print ISSN:
0950-1991
Electronic ISSN:
1477-9129
Topics:
Biology
Keywords:
Chromatin & epigenetics, Reproductive biology
Published by:
http://www.biologists.com/
_version_ 1836399101348937730
autor Mochizuki, K., Tando, Y., Sekinaka, T., Otsuka, K., Hayashi, Y., Kobayashi, H., Kamio, A., Ito-Matsuoka, Y., Takehara, A., Kono, T., Osumi, N., Matsui, Y.
beschreibung Kentaro Mochizuki, Yukiko Tando, Tamotsu Sekinaka, Kei Otsuka, Yohei Hayashi, Hisato Kobayashi, Asuka Kamio, Yumi Ito-Matsuoka, Asuka Takehara, Tomohiro Kono, Noriko Osumi, and Yasuhisa Matsui In mouse embryos, primordial germ cells (PGCs) are fate-determined from epiblast cells. Signaling pathways involved in PGC formation have been identified, but their epigenetic mechanisms remain poorly understood. Here, we show that the histone methyltransferase SETDB1 is an epigenetic regulator of PGC fate determination. Setdb1 -deficient embryos exhibit drastic reduction of nascent PGCs. Dppa2 , Otx2 and Utf1 are de-repressed whereas mesoderm development-related genes, including BMP4 signaling-related genes, are downregulated by Setdb1 knockdown during PGC-like cell (PGCLC) induction. In addition, binding of SETDB1 is observed at the flanking regions of Dppa2 , Otx2 and Utf1 in cell aggregates containing PGCLCs, and trimethylation of lysine 9 of histone H3 is reduced by Setdb1 knockdown at those regions. Furthermore, DPPA2, OTX2 and UTF1 binding is increased in genes encoding BMP4 signaling-related proteins, including SMAD1. Finally, overexpression of Dppa2 , Otx2 and Utf1 in cell aggregates containing PGCLCs results in the repression of BMP4 signaling-related genes and PGC determinant genes. We propose that the localization of SETDB1 to Dppa2 , Otx2 and Utf1 , and subsequent repression of their expression, are crucial for PGC determination by ensuring BMP4 signaling.
citation_standardnr 6367253
datenlieferant ipn_articles
feed_id 1748
feed_publisher The Company of Biologists
feed_publisher_url http://www.biologists.com/
insertion_date 2018-12-11
journaleissn 1477-9129
journalissn 0950-1991
publikationsjahr_anzeige 2018
publikationsjahr_facette 2018
publikationsjahr_intervall 7984:2015-2019
publikationsjahr_sort 2018
publisher The Company of Biologists
quelle Development
relation http://dev.biologists.org/cgi/content/short/145/23/dev164160?rss=1
schlagwort Chromatin & epigenetics, Reproductive biology
search_space articles
shingle_author_1 Mochizuki, K., Tando, Y., Sekinaka, T., Otsuka, K., Hayashi, Y., Kobayashi, H., Kamio, A., Ito-Matsuoka, Y., Takehara, A., Kono, T., Osumi, N., Matsui, Y.
shingle_author_2 Mochizuki, K., Tando, Y., Sekinaka, T., Otsuka, K., Hayashi, Y., Kobayashi, H., Kamio, A., Ito-Matsuoka, Y., Takehara, A., Kono, T., Osumi, N., Matsui, Y.
shingle_author_3 Mochizuki, K., Tando, Y., Sekinaka, T., Otsuka, K., Hayashi, Y., Kobayashi, H., Kamio, A., Ito-Matsuoka, Y., Takehara, A., Kono, T., Osumi, N., Matsui, Y.
shingle_author_4 Mochizuki, K., Tando, Y., Sekinaka, T., Otsuka, K., Hayashi, Y., Kobayashi, H., Kamio, A., Ito-Matsuoka, Y., Takehara, A., Kono, T., Osumi, N., Matsui, Y.
shingle_catch_all_1 SETDB1 is essential for mouse primordial germ cell fate determination by ensuring BMP signaling [RESEARCH ARTICLE]
Chromatin & epigenetics, Reproductive biology
Kentaro Mochizuki, Yukiko Tando, Tamotsu Sekinaka, Kei Otsuka, Yohei Hayashi, Hisato Kobayashi, Asuka Kamio, Yumi Ito-Matsuoka, Asuka Takehara, Tomohiro Kono, Noriko Osumi, and Yasuhisa Matsui In mouse embryos, primordial germ cells (PGCs) are fate-determined from epiblast cells. Signaling pathways involved in PGC formation have been identified, but their epigenetic mechanisms remain poorly understood. Here, we show that the histone methyltransferase SETDB1 is an epigenetic regulator of PGC fate determination. Setdb1 -deficient embryos exhibit drastic reduction of nascent PGCs. Dppa2 , Otx2 and Utf1 are de-repressed whereas mesoderm development-related genes, including BMP4 signaling-related genes, are downregulated by Setdb1 knockdown during PGC-like cell (PGCLC) induction. In addition, binding of SETDB1 is observed at the flanking regions of Dppa2 , Otx2 and Utf1 in cell aggregates containing PGCLCs, and trimethylation of lysine 9 of histone H3 is reduced by Setdb1 knockdown at those regions. Furthermore, DPPA2, OTX2 and UTF1 binding is increased in genes encoding BMP4 signaling-related proteins, including SMAD1. Finally, overexpression of Dppa2 , Otx2 and Utf1 in cell aggregates containing PGCLCs results in the repression of BMP4 signaling-related genes and PGC determinant genes. We propose that the localization of SETDB1 to Dppa2 , Otx2 and Utf1 , and subsequent repression of their expression, are crucial for PGC determination by ensuring BMP4 signaling.
Mochizuki, K., Tando, Y., Sekinaka, T., Otsuka, K., Hayashi, Y., Kobayashi, H., Kamio, A., Ito-Matsuoka, Y., Takehara, A., Kono, T., Osumi, N., Matsui, Y.
The Company of Biologists
0950-1991
09501991
1477-9129
14779129
shingle_catch_all_2 SETDB1 is essential for mouse primordial germ cell fate determination by ensuring BMP signaling [RESEARCH ARTICLE]
Chromatin & epigenetics, Reproductive biology
Kentaro Mochizuki, Yukiko Tando, Tamotsu Sekinaka, Kei Otsuka, Yohei Hayashi, Hisato Kobayashi, Asuka Kamio, Yumi Ito-Matsuoka, Asuka Takehara, Tomohiro Kono, Noriko Osumi, and Yasuhisa Matsui In mouse embryos, primordial germ cells (PGCs) are fate-determined from epiblast cells. Signaling pathways involved in PGC formation have been identified, but their epigenetic mechanisms remain poorly understood. Here, we show that the histone methyltransferase SETDB1 is an epigenetic regulator of PGC fate determination. Setdb1 -deficient embryos exhibit drastic reduction of nascent PGCs. Dppa2 , Otx2 and Utf1 are de-repressed whereas mesoderm development-related genes, including BMP4 signaling-related genes, are downregulated by Setdb1 knockdown during PGC-like cell (PGCLC) induction. In addition, binding of SETDB1 is observed at the flanking regions of Dppa2 , Otx2 and Utf1 in cell aggregates containing PGCLCs, and trimethylation of lysine 9 of histone H3 is reduced by Setdb1 knockdown at those regions. Furthermore, DPPA2, OTX2 and UTF1 binding is increased in genes encoding BMP4 signaling-related proteins, including SMAD1. Finally, overexpression of Dppa2 , Otx2 and Utf1 in cell aggregates containing PGCLCs results in the repression of BMP4 signaling-related genes and PGC determinant genes. We propose that the localization of SETDB1 to Dppa2 , Otx2 and Utf1 , and subsequent repression of their expression, are crucial for PGC determination by ensuring BMP4 signaling.
Mochizuki, K., Tando, Y., Sekinaka, T., Otsuka, K., Hayashi, Y., Kobayashi, H., Kamio, A., Ito-Matsuoka, Y., Takehara, A., Kono, T., Osumi, N., Matsui, Y.
The Company of Biologists
0950-1991
09501991
1477-9129
14779129
shingle_catch_all_3 SETDB1 is essential for mouse primordial germ cell fate determination by ensuring BMP signaling [RESEARCH ARTICLE]
Chromatin & epigenetics, Reproductive biology
Kentaro Mochizuki, Yukiko Tando, Tamotsu Sekinaka, Kei Otsuka, Yohei Hayashi, Hisato Kobayashi, Asuka Kamio, Yumi Ito-Matsuoka, Asuka Takehara, Tomohiro Kono, Noriko Osumi, and Yasuhisa Matsui In mouse embryos, primordial germ cells (PGCs) are fate-determined from epiblast cells. Signaling pathways involved in PGC formation have been identified, but their epigenetic mechanisms remain poorly understood. Here, we show that the histone methyltransferase SETDB1 is an epigenetic regulator of PGC fate determination. Setdb1 -deficient embryos exhibit drastic reduction of nascent PGCs. Dppa2 , Otx2 and Utf1 are de-repressed whereas mesoderm development-related genes, including BMP4 signaling-related genes, are downregulated by Setdb1 knockdown during PGC-like cell (PGCLC) induction. In addition, binding of SETDB1 is observed at the flanking regions of Dppa2 , Otx2 and Utf1 in cell aggregates containing PGCLCs, and trimethylation of lysine 9 of histone H3 is reduced by Setdb1 knockdown at those regions. Furthermore, DPPA2, OTX2 and UTF1 binding is increased in genes encoding BMP4 signaling-related proteins, including SMAD1. Finally, overexpression of Dppa2 , Otx2 and Utf1 in cell aggregates containing PGCLCs results in the repression of BMP4 signaling-related genes and PGC determinant genes. We propose that the localization of SETDB1 to Dppa2 , Otx2 and Utf1 , and subsequent repression of their expression, are crucial for PGC determination by ensuring BMP4 signaling.
Mochizuki, K., Tando, Y., Sekinaka, T., Otsuka, K., Hayashi, Y., Kobayashi, H., Kamio, A., Ito-Matsuoka, Y., Takehara, A., Kono, T., Osumi, N., Matsui, Y.
The Company of Biologists
0950-1991
09501991
1477-9129
14779129
shingle_catch_all_4 SETDB1 is essential for mouse primordial germ cell fate determination by ensuring BMP signaling [RESEARCH ARTICLE]
Chromatin & epigenetics, Reproductive biology
Kentaro Mochizuki, Yukiko Tando, Tamotsu Sekinaka, Kei Otsuka, Yohei Hayashi, Hisato Kobayashi, Asuka Kamio, Yumi Ito-Matsuoka, Asuka Takehara, Tomohiro Kono, Noriko Osumi, and Yasuhisa Matsui In mouse embryos, primordial germ cells (PGCs) are fate-determined from epiblast cells. Signaling pathways involved in PGC formation have been identified, but their epigenetic mechanisms remain poorly understood. Here, we show that the histone methyltransferase SETDB1 is an epigenetic regulator of PGC fate determination. Setdb1 -deficient embryos exhibit drastic reduction of nascent PGCs. Dppa2 , Otx2 and Utf1 are de-repressed whereas mesoderm development-related genes, including BMP4 signaling-related genes, are downregulated by Setdb1 knockdown during PGC-like cell (PGCLC) induction. In addition, binding of SETDB1 is observed at the flanking regions of Dppa2 , Otx2 and Utf1 in cell aggregates containing PGCLCs, and trimethylation of lysine 9 of histone H3 is reduced by Setdb1 knockdown at those regions. Furthermore, DPPA2, OTX2 and UTF1 binding is increased in genes encoding BMP4 signaling-related proteins, including SMAD1. Finally, overexpression of Dppa2 , Otx2 and Utf1 in cell aggregates containing PGCLCs results in the repression of BMP4 signaling-related genes and PGC determinant genes. We propose that the localization of SETDB1 to Dppa2 , Otx2 and Utf1 , and subsequent repression of their expression, are crucial for PGC determination by ensuring BMP4 signaling.
Mochizuki, K., Tando, Y., Sekinaka, T., Otsuka, K., Hayashi, Y., Kobayashi, H., Kamio, A., Ito-Matsuoka, Y., Takehara, A., Kono, T., Osumi, N., Matsui, Y.
The Company of Biologists
0950-1991
09501991
1477-9129
14779129
shingle_title_1 SETDB1 is essential for mouse primordial germ cell fate determination by ensuring BMP signaling [RESEARCH ARTICLE]
shingle_title_2 SETDB1 is essential for mouse primordial germ cell fate determination by ensuring BMP signaling [RESEARCH ARTICLE]
shingle_title_3 SETDB1 is essential for mouse primordial germ cell fate determination by ensuring BMP signaling [RESEARCH ARTICLE]
shingle_title_4 SETDB1 is essential for mouse primordial germ cell fate determination by ensuring BMP signaling [RESEARCH ARTICLE]
timestamp 2025-06-30T23:37:36.967Z
titel SETDB1 is essential for mouse primordial germ cell fate determination by ensuring BMP signaling [RESEARCH ARTICLE]
titel_suche SETDB1 is essential for mouse primordial germ cell fate determination by ensuring BMP signaling [RESEARCH ARTICLE]
topic W
uid ipn_articles_6367253