title: Eμand 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 cluster: the 5'Eμsuper-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, Eμin contrast likely falls under control of the 3'RR.
authors.affiliation: CNRS UMR 7276, CRIBL, Université de Limoges, Limoges, France. alexis.saintamand@live.fr.|INSERM U1236, Université Rennes 1, Rennes, France. alexis.saintamand@live.fr.
authors.forename: A
authors.initials: A
authors.lastname: Saintamand
authors.affiliation: CNRS UMR 7276, CRIBL, Université de Limoges, Limoges, France.
authors.forename: C
authors.initials: C
authors.lastname: Vincent-Fabert
authors.affiliation: CNRS UMR 7276, CRIBL, Université de Limoges, Limoges, France.
authors.forename: M
authors.initials: M
authors.lastname: Marquet
authors.affiliation: CNRS UMR 7276, CRIBL, Université de Limoges, Limoges, France.
authors.forename: N
authors.initials: N
authors.lastname: Ghazzaui
authors.affiliation: CNRS et Université de Nice Sophia Antipolis, Institut de Pharmacologie Moléculaire et Cellulaire, UMR 6097, Sophia, Antipolis, France.
authors.forename: V
authors.initials: V
authors.lastname: Magnone
authors.affiliation: CNRS UMR 7276, CRIBL, Université de Limoges, Limoges, France.
authors.forename: E
authors.initials: E
authors.lastname: Pinaud
authors.affiliation: CNRS UMR 7276, CRIBL, Université de Limoges, Limoges, France.
authors.forename: M
authors.initials: M
authors.lastname: Cogné
authors.affiliation: CNRS UMR 7276, CRIBL, Université de Limoges, Limoges, France. yves.denizot@unilim.fr.
authors.forename: Y
authors.initials: Y
authors.lastname: Denizot
mesh_terms: D000818:Animals; D001402:B-Lymphocytes / Q000166:cytology* / Q000378:metabolism*; D002454:Cell Differentiation / Q000235:genetics*; D004742:Enhancer Elements, Genetic; D044127:Epigenesis, Genetic; D005260:Female; D017578:Immunoglobulin Class Switching / Q000235:genetics; D007143:Immunoglobulin Heavy Chains / Q000235:genetics*; D008297:Male; D051379:Mice; D014158:Transcription, Genetic
chemical_list: D007143:Immunoglobulin Heavy Chains