PRC1 coordinates timing of sexual differentiation of female primordial germ cells
The Polycomb repressive complex 1 (PRC1) is found to have important gene-dosage-dependent and sex-specific roles in primordial germ cell (PGC) development, including the maintenance of high levels of Oct4 and Nanog and ensuring the proper timing of meiosis through the suppression of retinoic acid si...
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| Vydáno v: | Nature (London) Ročník 495; číslo 7440; s. 236 - 240 |
|---|---|
| Hlavní autoři: | , , , , , , , , |
| Médium: | Journal Article |
| Jazyk: | angličtina |
| Vydáno: |
London
Nature Publishing Group UK
14.03.2013
Nature Publishing Group |
| Témata: | |
| ISSN: | 0028-0836, 1476-4687, 1476-4687 |
| On-line přístup: | Získat plný text |
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| Shrnutí: | The Polycomb repressive complex 1 (PRC1) is found to have important gene-dosage-dependent and sex-specific roles in primordial germ cell (PGC) development, including the maintenance of high levels of
Oct4
and
Nanog
and ensuring the proper timing of meiosis through the suppression of retinoic acid signalling in female PGCs.
PRC1 role in germ cell development
Polycomb group proteins are involved in the transcriptional repression of developmental regulators in embryonic stem cells, where they maintain pluripotency and cell identity during subsequent development. Antoine Peters and colleagues have studied the function of the Polycomb repressive complex 1 (PRC1) in the development of mouse primordial germ cells (PGCs). They observed multiple sex-specific roles of PRC1 in development. PRC1 is required for the maintenance of high levels of expression of the transcription factors Oct4 and Nanog. And by suppressing retinoic acid signalling provided by the somatic compartment of the female genital ridge, PRC1 also ensures proper timing of meiotic induction.
In mammals, sex differentiation of primordial germ cells (PGCs) is determined by extrinsic cues from the environment
1
. In mouse female PGCs, expression of stimulated by retinoic acid gene 8 (
Stra8
) and meiosis are induced in response to retinoic acid provided from the mesonephroi
2
,
3
,
4
,
5
. Given the widespread role of retinoic acid signalling during development
6
,
7
, the molecular mechanisms that enable PGCs to express
Stra8
and enter meiosis in a timely manner are unknown
2
,
8
. Here we identify gene-dosage-dependent roles in PGC development for
Ring1
and
Rnf2
, two central components of the Polycomb repressive complex 1 (PRC1)
9
,
10
. Both paralogues are essential for PGC development between days 10.5 and 11.5 of gestation.
Rnf2
is subsequently required in female PGCs to maintain high levels of
Oct4
(also known as
Pou5f1
) and
Nanog
expression
11
, and to prevent premature induction of meiotic gene expression and entry into meiotic prophase. Chemical inhibition of retinoic acid signalling partially suppresses precocious
Oct4
downregulation and
Stra8
activation in
Rnf2
-deficient female PGCs. Chromatin immunoprecipitation analyses show that
Stra8
is a direct target of PRC1 and PRC2 in PGCs. These data demonstrate the importance of PRC1 gene dosage in PGC development and in coordinating the timing of sex differentiation of female PGCs by antagonizing extrinsic retinoic acid signalling. |
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| Bibliografie: | ObjectType-Article-2 SourceType-Scholarly Journals-1 ObjectType-Feature-1 content type line 14 ObjectType-Article-1 ObjectType-Feature-2 content type line 23 |
| ISSN: | 0028-0836 1476-4687 1476-4687 |
| DOI: | 10.1038/nature11918 |