Regulation of immune signal integration and memory by inflammation-induced chromosome conformation
6 affiliations
- 14D Nucleome Consortium, National Institutes of Health
- 2Center for Personal Dynamic Regulomes, Stanford University
- 3Department of Pathology, Stanford University
- 4Department of Bioengineering, Stanford University
- 5HHMI, Stanford University
- 6Parker Institute for Cancer Immunotherapy
Abstract
3-dimensional (3D) genome conformation is central to gene expression regulation, yet our understanding of its contribution to rapid transcriptional responses, signal integration, and memory in immune cells is limited. Here, we study the molecular regulation of the inflammatory response in primary macrophages using integrated transcriptomic, epigenomic, and chromosome conformation data, including base pair-resolution Micro-Capture C. We demonstrate that interleukin-4 (IL-4) primes the inflammatory response in macrophages by stably rewiring 3D genome conformation, juxtaposing endotoxin-, interferon-gamma-, and dexamethasone-responsive enhancers in close proximity to their cognate gene promoters. CRISPR-based perturbations of enhancer-promoter contacts or CCCTC-binding factor (CTCF) boundary elements demonstrated that IL-4-driven conformation changes are indispensable for enhanced and synergistic endotoxin-induced transcriptional responses, as well as transcriptional memory following stimulus removal. Moreover, transcriptional memory mediated by changes in chromosome conformation often occurred in the absence of changes in chromatin accessibility or histone modifications. Collectively, these findings demonstrate that rapid and memory transcriptional responses to immunological stimuli are encoded in the 3D genome.
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BibTeX
@article{daniel2026regulation,
title = {{Regulation of immune signal integration and memory by inflammation-induced chromosome conformation}},
author = {Bence Dániel and Andy Y. Chen and Katalin D. Sandor and Wenxi Zhang and Zhuang Miao and Kathryn E. Yost and Caleb A. Lareau and Howard Y. Chang and Ansuman T. Satpathy},
journal = {Proceedings of the National Academy of Sciences},
year = {2026},
month = sep,
doi = {10.1073/pnas.2600693123},
url = {https://doi.org/10.1073/pnas.2600693123},
note = {CC BY},
}
RIS
TY - JOUR
TI - Regulation of immune signal integration and memory by inflammation-induced chromosome conformation
AU - Bence Dániel
AU - Andy Y. Chen
AU - Katalin D. Sandor
AU - Wenxi Zhang
AU - Zhuang Miao
AU - Kathryn E. Yost
AU - Caleb A. Lareau
AU - Howard Y. Chang
AU - Ansuman T. Satpathy
PY - 2026
DA - 2026/09/15
JO - Proceedings of the National Academy of Sciences
DO - 10.1073/pnas.2600693123
UR - https://doi.org/10.1073/pnas.2600693123
AB - 3-dimensional (3D) genome conformation is central to gene expression regulation, yet our understanding of its contribution to rapid transcriptional responses, signal integration, and memory in immune cells is limited. Here, we study the molecular regulation of the inflammatory response in primary macrophages using integrated transcriptomic, epigenomic, and chromosome conformation data, including base pair-resolution Micro-Capture C. We demonstrate that interleukin-4 (IL-4) primes the inflammatory response in macrophages by stably rewiring 3D genome conformation, juxtaposing endotoxin-, interferon-gamma-, and dexamethasone-responsive enhancers in close proximity to their cognate gene promoters. CRISPR-based perturbations of enhancer-promoter contacts or CCCTC-binding factor (CTCF) boundary elements demonstrated that IL-4-driven conformation changes are indispensable for enhanced and synergistic endotoxin-induced transcriptional responses, as well as transcriptional memory following stimulus removal. Moreover, transcriptional memory mediated by changes in chromosome conformation often occurred in the absence of changes in chromatin accessibility or histone modifications. Collectively, these findings demonstrate that rapid and memory transcriptional responses to immunological stimuli are encoded in the 3D genome.
SN - 0027-8424
SN - 1091-6490
ER -