Eμ and 3′RR IgH enhancers show hierarchic unilateral dependence in mature B-cells

Abstract Enhancer and super-enhancers are master regulators of cell fate. While they act at long-distances on adjacent genes, it is unclear whether they also act on one another. The immunoglobulin heavy chain (IgH) locus is unique in carrying two super-enhancers at both ends of the constant gene clu...

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Autores principales:	A. Saintamand, C. Vincent-Fabert, M. Marquet, N. Ghazzaui, V. Magnone, E. Pinaud, M. Cogné, Y. Denizot
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/759dce4b4ff54191badca142fafe61e7
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spelling	oai:doaj.org-article:759dce4b4ff54191badca142fafe61e72021-12-02T12:32:39ZEμ and 3′RR IgH enhancers show hierarchic unilateral dependence in mature B-cells10.1038/s41598-017-00575-02045-2322https://doaj.org/article/759dce4b4ff54191badca142fafe61e72017-03-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-00575-0https://doaj.org/toc/2045-2322Abstract Enhancer and super-enhancers are master regulators of cell fate. While they act at long-distances on adjacent genes, it is unclear whether they also act on one another. The immunoglobulin heavy chain (IgH) locus is unique in carrying two super-enhancers at both ends of the constant gene cluster: the 5′Eμ super-enhancer promotes VDJ recombination during the earliest steps of B-cell ontogeny while the 3′ regulatory region (3′RR) is essential for late differentiation. Since they carry functional synergies in mature B-cells and physically interact during IgH locus DNA looping, we investigated if they were independent engines of locus remodelling or if their function was more intimately intermingled, their optimal activation then requiring physical contact with each other. Analysis of chromatin marks, enhancer RNA transcription and accessibility in Eμ- and 3′RR-deficient mice show, in mature activated B-cells, an unilateral dependence of this pair of enhancers: while the 3′RR acts in autonomy, Eμ in contrast likely falls under control of the 3′RR.A. SaintamandC. Vincent-FabertM. MarquetN. GhazzauiV. MagnoneE. PinaudM. CognéY. DenizotNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-7 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q A. Saintamand C. Vincent-Fabert M. Marquet N. Ghazzaui V. Magnone E. Pinaud M. Cogné Y. Denizot Eμ and 3′RR IgH enhancers show hierarchic unilateral dependence in mature B-cells
description	Abstract Enhancer and super-enhancers are master regulators of cell fate. While they act at long-distances on adjacent genes, it is unclear whether they also act on one another. The immunoglobulin heavy chain (IgH) locus is unique in carrying two super-enhancers at both ends of the constant gene cluster: the 5′Eμ super-enhancer promotes VDJ recombination during the earliest steps of B-cell ontogeny while the 3′ regulatory region (3′RR) is essential for late differentiation. Since they carry functional synergies in mature B-cells and physically interact during IgH locus DNA looping, we investigated if they were independent engines of locus remodelling or if their function was more intimately intermingled, their optimal activation then requiring physical contact with each other. Analysis of chromatin marks, enhancer RNA transcription and accessibility in Eμ- and 3′RR-deficient mice show, in mature activated B-cells, an unilateral dependence of this pair of enhancers: while the 3′RR acts in autonomy, Eμ in contrast likely falls under control of the 3′RR.
format	article
author	A. Saintamand C. Vincent-Fabert M. Marquet N. Ghazzaui V. Magnone E. Pinaud M. Cogné Y. Denizot
author_facet	A. Saintamand C. Vincent-Fabert M. Marquet N. Ghazzaui V. Magnone E. Pinaud M. Cogné Y. Denizot
author_sort	A. Saintamand
title	Eμ and 3′RR IgH enhancers show hierarchic unilateral dependence in mature B-cells
title_short	Eμ and 3′RR IgH enhancers show hierarchic unilateral dependence in mature B-cells
title_full	Eμ and 3′RR IgH enhancers show hierarchic unilateral dependence in mature B-cells
title_fullStr	Eμ and 3′RR IgH enhancers show hierarchic unilateral dependence in mature B-cells
title_full_unstemmed	Eμ and 3′RR IgH enhancers show hierarchic unilateral dependence in mature B-cells
title_sort	eμ and 3′rr igh enhancers show hierarchic unilateral dependence in mature b-cells
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/759dce4b4ff54191badca142fafe61e7
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Eμ and 3′RR IgH enhancers show hierarchic unilateral dependence in mature B-cells

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