ArticleNucleic acids research2019
Labelled regulatory elements are pervasive features of the macrophage genome and are dynamically utilized by classical and alternative polarization signals.
Article in Nucleic acids research, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.
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Who cites it
9 citing papers in PubMed, 10 citations in OpenAlex.
- CpG content contributes to tissue-resident macrophage enhancer selection.Nucleic acids research · 2026Article
- Multifaceted regulatory mechanisms of the EGR family in tumours and prospects for therapeutic applications (Review).International journal of molecular medicine · 2025Review
- Genomic regions occupied by both RARα and VDR are involved in the convergence and cooperation of retinoid and vitamin D signaling pathways.Nucleic acids research · 2025Article
- BRD9 regulates interferon-stimulated genes during macrophage activation via cooperation with BET protein BRD4.Proceedings of the National Academy of Sciences of the United States of America · 2022Article
- Chromatin accessibility analysis identifies the transcription factor ETV5 as a suppressor of adipose tissue macrophage activation in obesity.Cell death & disease · 2021Article
- Transcriptional circuitry atlas of genetic diverse unstimulated murine and human macrophages define disparity in population-wide innate immunity.Scientific reports · 2021Article
- The alternative macrophage relay: STAT6 passes the baton to EGR2.Genes & development · 2020Article
- HDAC3 Mediates the Inflammatory Response and LPS Tolerance in Human Monocytes and Macrophages.Frontiers in immunology · 2020Article
- Unorthodox Transcriptional Mechanisms of Lipid-Sensing Nuclear Receptors in Macrophages: Are We Opening a New Chapter?Frontiers in endocrinology · 2020Review
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Authors and funding
15 authors at 5 institutions in 4 countries.
Funding
Abstract
The concept of tissue-specific gene expression posits that lineage-determining transcription factors (LDTFs) determine the open chromatin profile of a cell via collaborative binding, providing molecular beacons to signal-dependent transcription factors (SDTFs). However, the guiding principles of LDTF binding, chromatin accessibility and enhancer activity have not yet been systematically evaluated. We sought to study these features of the macrophage genome by the combination of experimental (ChIP-seq, ATAC-seq and GRO-seq) and computational approaches. We show that Random Forest and Support Vector Regression machine learning methods can accurately predict chromatin accessibility using the binding patterns of the LDTF PU.1 and four other key TFs of macrophages (IRF8, JUNB, CEBPA and RUNX1). Any of these TFs alone were not sufficient to predict open chromatin, indicating that TF binding is widespread at closed or weakly opened chromatin regions. Analysis of the PU.1 cistrome revealed that two-thirds of PU.1 binding occurs at low accessible chromatin. We termed these sites labelled regulatory elements (LREs), which may represent a dormant state of a future enhancer and contribute to macrophage cellular plasticity. Collectively, our work demonstrates the existence of LREs occupied by various key TFs, regulating specific gene expression programs triggered by divergent macrophage polarizing stimuli.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.