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Chromatin interaction-based annotation of regulatory elements reveals dynamic promoter-enhancer interactions in lymphocyte development

Tingvall-Gustafsson, Johanna LU orcid ; Jensen, Christina T. LU ; Ungerbäck, Jonas LU and Sigvardsson, Mikael LU (2025) In iScience 28(7).
Abstract

Stage- and lineage-specific gene expression patterns are controlled by a complex interplay between transcription factors, the epigenetic landscape, and the three-dimensional (3D) structure of the DNA. The 3D structure allows for the formation of DNA loops that juxtaposition distal regulatory elements to the promoters, allowing for tight control of gene expression. Developing a tool to facilitate the exploration of complex gene regulatory networks based on chromosome configuration data in early lymphocytes, we show that lineage-specific transcription factors target regulatory elements annotated to both lineage-specific and broadly expressed genes. Several regulatory elements annotated to lineage-specific genes were also annotated to... (More)

Stage- and lineage-specific gene expression patterns are controlled by a complex interplay between transcription factors, the epigenetic landscape, and the three-dimensional (3D) structure of the DNA. The 3D structure allows for the formation of DNA loops that juxtaposition distal regulatory elements to the promoters, allowing for tight control of gene expression. Developing a tool to facilitate the exploration of complex gene regulatory networks based on chromosome configuration data in early lymphocytes, we show that lineage-specific transcription factors target regulatory elements annotated to both lineage-specific and broadly expressed genes. Several regulatory elements annotated to lineage-specific genes were also annotated to alternative promoters in a context-dependent manner, revealing a highly complex interplay between promoters and DREs in early lymphocyte development. These data highlight how efficient annotation procedures for linking distal regulatory elements to target genes provide valuable insights into gene regulatory networks.

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author
; ; and
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Chromosome organization, Components of the immune system, Epigenetics, Molecular genetics
in
iScience
volume
28
issue
7
article number
112855
publisher
Elsevier
external identifiers
  • scopus:105010094429
  • pmid:40687796
ISSN
2589-0042
DOI
10.1016/j.isci.2025.112855
language
English
LU publication?
yes
additional info
Publisher Copyright: © 2025 The Author(s)
id
edf8fba1-63b0-490f-8ecf-9a940468e712
date added to LUP
2025-12-05 15:34:23
date last changed
2025-12-06 03:00:02
@article{edf8fba1-63b0-490f-8ecf-9a940468e712,
  abstract     = {{<p>Stage- and lineage-specific gene expression patterns are controlled by a complex interplay between transcription factors, the epigenetic landscape, and the three-dimensional (3D) structure of the DNA. The 3D structure allows for the formation of DNA loops that juxtaposition distal regulatory elements to the promoters, allowing for tight control of gene expression. Developing a tool to facilitate the exploration of complex gene regulatory networks based on chromosome configuration data in early lymphocytes, we show that lineage-specific transcription factors target regulatory elements annotated to both lineage-specific and broadly expressed genes. Several regulatory elements annotated to lineage-specific genes were also annotated to alternative promoters in a context-dependent manner, revealing a highly complex interplay between promoters and DREs in early lymphocyte development. These data highlight how efficient annotation procedures for linking distal regulatory elements to target genes provide valuable insights into gene regulatory networks.</p>}},
  author       = {{Tingvall-Gustafsson, Johanna and Jensen, Christina T. and Ungerbäck, Jonas and Sigvardsson, Mikael}},
  issn         = {{2589-0042}},
  keywords     = {{Chromosome organization; Components of the immune system; Epigenetics; Molecular genetics}},
  language     = {{eng}},
  month        = {{07}},
  number       = {{7}},
  publisher    = {{Elsevier}},
  series       = {{iScience}},
  title        = {{Chromatin interaction-based annotation of regulatory elements reveals dynamic promoter-enhancer interactions in lymphocyte development}},
  url          = {{http://dx.doi.org/10.1016/j.isci.2025.112855}},
  doi          = {{10.1016/j.isci.2025.112855}},
  volume       = {{28}},
  year         = {{2025}},
}