» Articles » PMID: 23932714

Remodeling of the Enhancer Landscape During Macrophage Activation is Coupled to Enhancer Transcription

Overview
Journal Mol Cell
Publisher Cell Press
Specialty Cell Biology
Date 2013 Aug 13
PMID 23932714
Citations 393
Authors
Affiliations
Soon will be listed here.
Abstract

Recent studies suggest a hierarchical model in which lineage-determining factors act in a collaborative manner to select and prime cell-specific enhancers, thereby enabling signal-dependent transcription factors to bind and function in a cell-type-specific manner. Consistent with this model, TLR4 signaling primarily regulates macrophage gene expression through a pre-existing enhancer landscape. However, TLR4 signaling also induces priming of ∼3,000 enhancer-like regions de novo, enabling visualization of intermediates in enhancer selection and activation. Unexpectedly, we find that enhancer transcription precedes local mono- and dimethylation of histone H3 lysine 4 (H3K4me1/2). H3K4 methylation at de novo enhancers is primarily dependent on the histone methyltransferases Mll1, Mll2/4, and Mll3 and is significantly reduced by inhibition of RNA polymerase II elongation. Collectively, these findings suggest an essential role of enhancer transcription in H3K4me1/2 deposition at de novo enhancers that is independent of potential functions of the resulting eRNA transcripts.

Citing Articles

Innate Immune Memory is Stimulus Specific.

OFarrell A, Niu Z, Li J, Van Eyndhoven L, Sarma K, Raj A bioRxiv. 2025; .

PMID: 39896612 PMC: 11785108. DOI: 10.1101/2025.01.22.634275.


Biomolecular condensates in immune cell fate.

Kodali S, Sands C, Guo L, Huang Y, Di Stefano B Nat Rev Immunol. 2025; .

PMID: 39875604 DOI: 10.1038/s41577-025-01130-z.


NF-κB and TET2 promote macrophage reprogramming in hypoxia that overrides the immunosuppressive effects of the tumor microenvironment.

de la Calle-Fabregat C, Calafell-Segura J, Gardet M, Dunsmore G, Mulder K, Ciudad L Sci Adv. 2024; 10(38):eadq5226.

PMID: 39292770 PMC: 11409945. DOI: 10.1126/sciadv.adq5226.


CRISPR Screening of Transcribed Super-Enhancers Identifies Drivers of Triple-Negative Breast Cancer Progression.

Lewis M, King C, Wisniewska K, Regner M, Coffey A, Kelly M Cancer Res. 2024; 84(21):3684-3700.

PMID: 39186674 PMC: 11534545. DOI: 10.1158/0008-5472.CAN-23-3995.


TIANA: transcription factors cooperativity inference analysis with neural attention.

Li R, Han C, Glass C BMC Bioinformatics. 2024; 25(1):274.

PMID: 39174927 PMC: 11342676. DOI: 10.1186/s12859-024-05852-0.


References
1.
Kobori M, Yang Z, Gong D, Heissmeyer V, Zhu H, Jung Y . Wedelolactone suppresses LPS-induced caspase-11 expression by directly inhibiting the IKK complex. Cell Death Differ. 2003; 11(1):123-30. DOI: 10.1038/sj.cdd.4401325. View

2.
Melo C, Drost J, Wijchers P, van de Werken H, de Wit E, Vrielink J . eRNAs are required for p53-dependent enhancer activity and gene transcription. Mol Cell. 2013; 49(3):524-35. DOI: 10.1016/j.molcel.2012.11.021. View

3.
PERRY R, Kelley D . Inhibition of RNA synthesis by actinomycin D: characteristic dose-response of different RNA species. J Cell Physiol. 1970; 76(2):127-39. DOI: 10.1002/jcp.1040760202. View

4.
Ostuni R, Piccolo V, Barozzi I, Polletti S, Termanini A, Bonifacio S . Latent enhancers activated by stimulation in differentiated cells. Cell. 2013; 152(1-2):157-71. DOI: 10.1016/j.cell.2012.12.018. View

5.
De Santa F, Barozzi I, Mietton F, Ghisletti S, Polletti S, Tusi B . A large fraction of extragenic RNA pol II transcription sites overlap enhancers. PLoS Biol. 2010; 8(5):e1000384. PMC: 2867938. DOI: 10.1371/journal.pbio.1000384. View