An EGR1-dependent cascade modulates genome architecture at the CSF1R locus
File(s)
Published version
Author(s)
Type
Journal Article
Abstract
The organization and dynamics of chromatin are key to regulating gene expression during myeloid cell differentiation. Sequence-specific transcription factors initiate and maintain a complex network of enhancer-promoter contacts, which is supported by insulating elements and genome folding organizers such as CTCF and Cohesin. The spatial arrangement of enhancers and promoters, as well as their epigenetic state, drives cell and tissue-specific transcriptomes. Here we dissect the spatial, transcriptional, and epigenetic landscape of the colony stimulating factor 1 receptor (CSF1R) locus in monocytes and macrophages. CSF1R is a receptor tyrosine kinase that triggers the signaling cascade required for macrophage differentiation. Previous work showed that CSF1R expression is regulated by multiple enhancers, including the fms-intronic regulatory element (FIRE). Here, we find that a single EGR-1 binding motif dictates activation of CSF1R. We also discover that the CSF1R entire locus folds into a hub of gene regulation, affecting an extended network of myeloid and inflammatory genes. Globally, EGR1 may have an expanded role as a macrophage-specific boundary element, supporting enhancer-promoter looping at several genes. In sum, we describe a novel 3D chromatin network that is critical for macrophage development and function.
Date Issued
2026-01-27
Date Acceptance
2025-12-08
Citation
Nucleic Acids Research, 2026, 54 (2)
ISSN
0305-1048
Publisher
Oxford University Press (OUP)
Start Page
gkaf1496
Journal / Book Title
Nucleic Acids Research
Volume
54
Issue
2
Copyright Statement
Published by Oxford University Press 2026. This work is written by (a) US Government employee(s) and is in the public domain in the US.
Identifier
https://www.ncbi.nlm.nih.gov/pubmed/41538316
PII: 8426366
Subjects
Early Growth Response Protein 1
Receptors, Granulocyte-Macrophage Colony-Stimulating Factor
Macrophages
Promoter Regions, Genetic
Enhancer Elements, Genetic
Animals
Humans
Mice
Gene Expression Regulation
Monocytes
Cell Differentiation
Chromatin
Genetic Loci
Epigenesis, Genetic
Binding Sites
Receptor, Macrophage Colony-Stimulating Factor
Publication Status
Published
Coverage Spatial
England
Article Number
gkaf1496
Date Publish Online
2026-01-15