title: Enhancer repertoires are reshaped independently of early priming and heterochromatin dynamics during B cell differentiation.
abstract: A widely accepted model posits that activation of enhancers during differentiation goes through a priming step prior to lineage commitment. To investigate the chronology of enhancer repertoire establishment during hematopoiesis, we monitored epigenome dynamics during three developmental stages representing hematopoietic stem cells, B-cell progenitors and mature B-cells. We find that only a minority of enhancers primed in stem cells or progenitors become active at later stages. Furthermore, most enhancers active in differentiated cells were not primed in earlier stages. Thus, the enhancer repertoire is reshaped dynamically during B-cell differentiation and enhancer priming in early stages does not appear to be an obligate step for enhancer activation. Furthermore, our data reveal that heterochromatin and Polycomb-mediated silencing have only a minor contribution in shaping enhancer repertoires during cell differentiation. Together, our data revisit the prevalent model about epigenetic reprogramming during hematopoiesis and give insights into the formation of gene regulatory networks.
authors.affiliation: Friedrich Miescher Institute for Biomedical Research, Maulbeerstrasse 66, 4058 Basel, Switzerland.
authors.forename: Mohamed-Amin
authors.initials: MA
authors.lastname: Choukrallah
authors.affiliation: Friedrich Miescher Institute for Biomedical Research, Maulbeerstrasse 66, 4058 Basel, Switzerland.
authors.forename: Shuang
authors.initials: S
authors.lastname: Song
authors.affiliation: Department of Biomedicine, University of Basel, Mattenstrasse 28, 4058 Basel, Switzerland.
authors.forename: Antonius G
authors.initials: AG
authors.lastname: Rolink
authors.affiliation: Friedrich Miescher Institute for Biomedical Research, Maulbeerstrasse 66, 4058 Basel, Switzerland.|Swiss Institute of Bioinformatics, Maulbeerstrasse 66, 4058 Basel, Switzerland.
authors.forename: Lukas
authors.initials: L
authors.lastname: Burger
authors.affiliation: Friedrich Miescher Institute for Biomedical Research, Maulbeerstrasse 66, 4058 Basel, Switzerland.|Faculty of Sciences, University of Basel, 4051 Basel, Switzerland.
authors.forename: Patrick
authors.initials: P
authors.lastname: Matthias
mesh_terms: D000818:Animals; D001402:B-Lymphocytes / Q000378:metabolism*; D047369:Chromatin Immunoprecipitation; D004742:Enhancer Elements, Genetic; D057890:Epigenomics; D020868:Gene Silencing; D006410:Hematopoiesis; D006412:Hematopoietic Stem Cells / Q000378:metabolism*; D006570:Heterochromatin / Q000378:metabolism; D006657:Histones / Q000378:metabolism*; D008810:Mice, Inbred C57BL; D063146:Polycomb-Group Proteins / Q000378:metabolism
chemical_list: D006570:Heterochromatin; D006657:Histones; D063146:Polycomb-Group Proteins