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B lymphocyte specification is preceded by extensive epigenetic priming in multipotent progenitors

Strid, Tobias LU ; Okuyama, Kazuki ; Tingvall-Gustafsson, Johanna LU orcid ; Kuruvilla, Jacob LU ; Jensen, Christina T. LU ; Lang, Stefan LU orcid ; Prasad, Mahadesh ; Somasundaram, Rajesh ; Åhsberg, Josefine LU and Cristobal, Susana , et al. (2021) In Journal of Immunology 206(11). p.2700-2713
Abstract

B lymphocyte development is dependent on the interplay between the chromatin landscape and lineage-specific transcription factors. It has been suggested that B lineage commitment is associated with major changes in the nuclear chromatin environment, proposing a critical role for lineage-specific transcription factors in the formation of the epigenetic landscape. In this report, we have used chromosome conformation capture in combination with assay for transposase-accessible chromatin sequencing analysis to enable highly efficient annotation of both proximal and distal transcriptional control elements to genes activated in B lineage specification in mice. A large majority of these genes were annotated to at least one regulatory element... (More)

B lymphocyte development is dependent on the interplay between the chromatin landscape and lineage-specific transcription factors. It has been suggested that B lineage commitment is associated with major changes in the nuclear chromatin environment, proposing a critical role for lineage-specific transcription factors in the formation of the epigenetic landscape. In this report, we have used chromosome conformation capture in combination with assay for transposase-accessible chromatin sequencing analysis to enable highly efficient annotation of both proximal and distal transcriptional control elements to genes activated in B lineage specification in mice. A large majority of these genes were annotated to at least one regulatory element with an accessible chromatin configuration in multipotent progenitors. Furthermore, the majority of binding sites for the key regulators of B lineage specification, EBF1 and PAX5, occurred in already accessible regions. EBF1 did, however, cause a dynamic change in assay for transposase-accessible chromatin accessibility and was critical for an increase in distal promoter-enhancer interactions. Our data unravel an extensive epigenetic priming at regulatory elements annotated to lineage-restricted genes and provide insight into the interplay between the epigenetic landscape and transcription factors in cell specification.

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organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Journal of Immunology
volume
206
issue
11
pages
14 pages
publisher
American Association of Immunologists
external identifiers
  • pmid:34021049
  • scopus:85107067456
ISSN
0022-1767
DOI
10.4049/jimmunol.2100048
language
English
LU publication?
yes
id
5c340cf8-c0b7-470a-a37c-da06007de336
date added to LUP
2022-01-04 15:01:40
date last changed
2024-06-01 23:00:44
@article{5c340cf8-c0b7-470a-a37c-da06007de336,
  abstract     = {{<p>B lymphocyte development is dependent on the interplay between the chromatin landscape and lineage-specific transcription factors. It has been suggested that B lineage commitment is associated with major changes in the nuclear chromatin environment, proposing a critical role for lineage-specific transcription factors in the formation of the epigenetic landscape. In this report, we have used chromosome conformation capture in combination with assay for transposase-accessible chromatin sequencing analysis to enable highly efficient annotation of both proximal and distal transcriptional control elements to genes activated in B lineage specification in mice. A large majority of these genes were annotated to at least one regulatory element with an accessible chromatin configuration in multipotent progenitors. Furthermore, the majority of binding sites for the key regulators of B lineage specification, EBF1 and PAX5, occurred in already accessible regions. EBF1 did, however, cause a dynamic change in assay for transposase-accessible chromatin accessibility and was critical for an increase in distal promoter-enhancer interactions. Our data unravel an extensive epigenetic priming at regulatory elements annotated to lineage-restricted genes and provide insight into the interplay between the epigenetic landscape and transcription factors in cell specification.</p>}},
  author       = {{Strid, Tobias and Okuyama, Kazuki and Tingvall-Gustafsson, Johanna and Kuruvilla, Jacob and Jensen, Christina T. and Lang, Stefan and Prasad, Mahadesh and Somasundaram, Rajesh and Åhsberg, Josefine and Cristobal, Susana and Soneji, Shamit and Ungerback, Jonas and Sigvardsson, Mikael}},
  issn         = {{0022-1767}},
  language     = {{eng}},
  number       = {{11}},
  pages        = {{2700--2713}},
  publisher    = {{American Association of Immunologists}},
  series       = {{Journal of Immunology}},
  title        = {{B lymphocyte specification is preceded by extensive epigenetic priming in multipotent progenitors}},
  url          = {{http://dx.doi.org/10.4049/jimmunol.2100048}},
  doi          = {{10.4049/jimmunol.2100048}},
  volume       = {{206}},
  year         = {{2021}},
}