Universität zu Köln

Bleckwehl, Tore, Crispatzu, Giuliano, Schaaf, Kaitlin, Respuela, Patricia, Bartusel, Michaela ORCID: 0000-0003-1008-1951, Benson, Laura, Clark, Stephen J., Dorighi, Kristel M., Barral, Antonio, Laugsch, Magdalena, van Ijcken, Wilfred F. J., Manzanares, Miguel ORCID: 0000-0003-4849-2836, Wysocka, Joanna, Reikf, Wolf and Rada-Iglesias, Alvaro ORCID: 0000-0001-7137-1341 (2021). Enhancer-associated H3K4 methylation safeguards in vitro germline competence. Nat. Commun., 12 (1). BERLIN: NATURE PORTFOLIO. ISSN 2041-1723

Full text not available from this repository.

Abstract

Germline specification in mammals occurs through an inductive process whereby competent cells in the post-implantation epiblast differentiate into primordial germ cells (PGC). The intrinsic factors that endow epiblast cells with the competence to respond to germline inductive signals remain unknown. Single-cell RNA sequencing across multiple stages of an in vitro PGC-like cells (PGCLC) differentiation system shows that PGCLC genes initially expressed in the naive pluripotent stage become homogeneously dismantled in germline competent epiblast like-cells (EpiLC). In contrast, the decommissioning of enhancers associated with these germline genes is incomplete. Namely, a subset of these enhancers partly retain H3K4me1, accumulate less heterochromatic marks and remain accessible and responsive to transcriptional activators. Subsequently, as in vitro germline competence is lost, these enhancers get further decommissioned and lose their responsiveness to transcriptional activators. Importantly, using H3K4me1-deficient cells, we show that the loss of this histone modification reduces the germline competence of EpiLC and decreases PGCLC differentiation efficiency. Our work suggests that, although H3K4me1 might not be essential for enhancer function, it can facilitate the (re)activation of enhancers and the establishment of gene expression programs during specific developmental transitions. While inductive signals controlling germline specification are well characterized, the intrinsic factors that allow epiblast cells to respond to such signals remain largely unknown. Here the authors use in vitro differentiated primordial germ cells to show that partial retention of histone H3K4 monomethylation within relevant enhancers is important for germline competence and specification.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Bleckwehl, Tore UNSPECIFIED UNSPECIFIED UNSPECIFIED Crispatzu, Giuliano UNSPECIFIED UNSPECIFIED UNSPECIFIED Schaaf, Kaitlin UNSPECIFIED UNSPECIFIED UNSPECIFIED Respuela, Patricia UNSPECIFIED UNSPECIFIED UNSPECIFIED Bartusel, Michaela UNSPECIFIED orcid.org/0000-0003-1008-1951 UNSPECIFIED Benson, Laura UNSPECIFIED UNSPECIFIED UNSPECIFIED Clark, Stephen J. UNSPECIFIED UNSPECIFIED UNSPECIFIED Dorighi, Kristel M. UNSPECIFIED UNSPECIFIED UNSPECIFIED Barral, Antonio UNSPECIFIED UNSPECIFIED UNSPECIFIED Laugsch, Magdalena UNSPECIFIED UNSPECIFIED UNSPECIFIED van Ijcken, Wilfred F. J. UNSPECIFIED UNSPECIFIED UNSPECIFIED Manzanares, Miguel UNSPECIFIED orcid.org/0000-0003-4849-2836 UNSPECIFIED Wysocka, Joanna UNSPECIFIED UNSPECIFIED UNSPECIFIED Reikf, Wolf UNSPECIFIED UNSPECIFIED UNSPECIFIED Rada-Iglesias, Alvaro UNSPECIFIED orcid.org/0000-0001-7137-1341 UNSPECIFIED
URN:	urn:nbn:de:hbz:38-602791
DOI:	10.1038/s41467-021-26065-6
Journal or Publication Title:	Nat. Commun.
Volume:	12
Number:	1
Date:	2021
Publisher:	NATURE PORTFOLIO
Place of Publication:	BERLIN
ISSN:	2041-1723
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language CELL FATE DECISIONS; DNA METHYLATION; HISTONE H3; GROUND-STATE; NAIVE PLURIPOTENCY; READ ALIGNMENT; MOUSE; CHROMATIN; SPECIFICATION; TRANSCRIPTION Multiple languages Multidisciplinary Sciences Multiple languages
URI:	http://kups.ub.uni-koeln.de/id/eprint/60279