NF-κB and BRG1 Bind a Distal Regulatory Element in the IL-3/GM-CSF Locus

Overview

Journal Mol Immunol

Specialties Allergy & Immunology
Molecular Biology

Date 2011 Aug 12

PMID 21831442

Citations 14

Authors

Andrea L Wurster

Patricia Precht

Michael J Pazin

Affiliations

Soon will be listed here.

Abstract

We investigated gene regulation at the IL-3/GM-CSF gene cluster. We found BRG1, a SWI/SNF remodeling ATPase, bound a distal element, CNSa. BRG1 binding was strongest in differentiated, stimulated T helper cells, paralleling IL-3 and GM-CSF expression. Depletion of BRG1 reduced IL-3 and GM-CSF transcription. BAF-specific SWI/SNF subunits bound to this locus and regulated IL-3 expression. CNSa was in closed chromatin in fibroblasts, open chromatin in differentiated T helper cells, and moderately open chromatin in naïve (undifferentiated) T helper cells; BRG1 was required for the most open state. CNSa increased transcription of a reporter in an episomal expression system, in a BRG1-dependent manner. The NF-κB subunit RelA/p65 bound CNSa in activated T helper cells. Inhibition of NF-κB blocked BRG1 binding to CNSa, chromatin opening at CNSa, and activation of IL-3 and GM-CSF. Together, these findings suggest CNSa is a distal enhancer that binds BRG1 and NF-κB.

Citing Articles

Elevated GRO-α and IL-18 in serum and brain implicate the NLRP3 inflammasome in frontotemporal dementia.

Lok H, Katzeff J, Hodges J, Piguet O, Fu Y, Halliday G Sci Rep. 2023; 13(1):8942.

PMID: 37268663 PMC: 10238432. DOI: 10.1038/s41598-023-35945-4.

CD4 T cells require Ikaros to inhibit their differentiation toward a pathogenic cell fate.

Bernardi C, Maurer G, Ye T, Marchal P, Jost B, Wissler M Proc Natl Acad Sci U S A. 2021; 118(17).

PMID: 33893236 PMC: 8092604. DOI: 10.1073/pnas.2023172118.

Brg1 restrains the pro-inflammatory properties of ILC3s and modulates intestinal immunity.

Qi X, Qiu J, Chang J, Ji Y, Yang Q, Cui G Mucosal Immunol. 2020; 14(1):38-52.

PMID: 32612160 PMC: 7790751. DOI: 10.1038/s41385-020-0317-3.

Regulation of Lymphatic GM-CSF Expression by the E3 Ubiquitin Ligase Cbl-b.

Peer S, Cappellano G, Hermann-Kleiter N, Albrecht-Schgoer K, Hinterleitner R, Baier G Front Immunol. 2018; 9:2311.

PMID: 30349541 PMC: 6186797. DOI: 10.3389/fimmu.2018.02311.

Immuno-suppressive function of nucleus-transducible BAF57-ΔPH in T cell activation via degradation of endogenous BAF57.

Moon J, Lee H, Ho C, Shin J, Ghosh S, Kim J Int J Hematol. 2018; 108(4):375-383.

PMID: 29978433 DOI: 10.1007/s12185-018-2491-6.

References

Brettingham-Moore K, Sprod O, Chen X, Oakford P, Shannon M, Holloway A . Determinants of a transcriptionally competent environment at the GM-CSF promoter. Nucleic Acids Res. 2008; 36(8):2639-53. PMC: 2377420. DOI: 10.1093/nar/gkn117. View

Schnitzler G, Sif S, Kingston R . Human SWI/SNF interconverts a nucleosome between its base state and a stable remodeled state. Cell. 1998; 94(1):17-27. DOI: 10.1016/s0092-8674(00)81217-9. View

Gebuhr T, Kovalev G, Bultman S, Godfrey V, Su L, Magnuson T . The role of Brg1, a catalytic subunit of mammalian chromatin-remodeling complexes, in T cell development. J Exp Med. 2003; 198(12):1937-49. PMC: 2194157. DOI: 10.1084/jem.20030714. View

Christova R, Jones T, Wu P, Bolzer A, Costa-Pereira A, Watling D . P-STAT1 mediates higher-order chromatin remodelling of the human MHC in response to IFNgamma. J Cell Sci. 2007; 120(Pt 18):3262-70. DOI: 10.1242/jcs.012328. View

Landry J, Banerjee S, Taylor B, Aplan P, Singer A, Wu C . Chromatin remodeling complex NURF regulates thymocyte maturation. Genes Dev. 2011; 25(3):275-86. PMC: 3034902. DOI: 10.1101/gad.2007311. View

Lorch Y, Maier-Davis B, Kornberg R . Chromatin remodeling by nucleosome disassembly in vitro. Proc Natl Acad Sci U S A. 2006; 103(9):3090-3. PMC: 1413907. DOI: 10.1073/pnas.0511050103. View

Nie Z, Xue Y, Yang D, Zhou S, Deroo B, Archer T . A specificity and targeting subunit of a human SWI/SNF family-related chromatin-remodeling complex. Mol Cell Biol. 2000; 20(23):8879-88. PMC: 86543. DOI: 10.1128/MCB.20.23.8879-8888.2000. View

Agarwal S, Rao A . Long-range transcriptional regulation of cytokine gene expression. Curr Opin Immunol. 1998; 10(3):345-52. DOI: 10.1016/s0952-7915(98)80174-x. View

Precht P, Wurster A, Pazin M . The SNF2H chromatin remodeling enzyme has opposing effects on cytokine gene expression. Mol Immunol. 2010; 47(11-12):2038-46. PMC: 2891439. DOI: 10.1016/j.molimm.2010.04.009. View

10.

Agarwal S, Rao A . Modulation of chromatin structure regulates cytokine gene expression during T cell differentiation. Immunity. 1999; 9(6):765-75. DOI: 10.1016/s1074-7613(00)80642-1. View

11.

Bert A, Johnson B, Baxter E, Cockerill P . A modular enhancer is differentially regulated by GATA and NFAT elements that direct different tissue-specific patterns of nucleosome positioning and inducible chromatin remodeling. Mol Cell Biol. 2007; 27(8):2870-85. PMC: 1899937. DOI: 10.1128/MCB.02323-06. View

12.

Bowers S, Mirabella F, Calero-Nieto F, Valeaux S, Hadjur S, Baxter E . A conserved insulator that recruits CTCF and cohesin exists between the closely related but divergently regulated interleukin-3 and granulocyte-macrophage colony-stimulating factor genes. Mol Cell Biol. 2009; 29(7):1682-93. PMC: 2655614. DOI: 10.1128/MCB.01411-08. View

13.

Placek K, Gasparian S, Coffre M, Maiella S, Sechet E, Bianchi E . Integration of distinct intracellular signaling pathways at distal regulatory elements directs T-bet expression in human CD4+ T cells. J Immunol. 2009; 183(12):7743-51. DOI: 10.4049/jimmunol.0803812. View

14.

Ji H, Jiang H, Ma W, Johnson D, Myers R, Wong W . An integrated software system for analyzing ChIP-chip and ChIP-seq data. Nat Biotechnol. 2008; 26(11):1293-300. PMC: 2596672. DOI: 10.1038/nbt.1505. View

15.

Ramirez-Carrozzi V, Nazarian A, Li C, Gore S, Sridharan R, Imbalzano A . Selective and antagonistic functions of SWI/SNF and Mi-2beta nucleosome remodeling complexes during an inflammatory response. Genes Dev. 2006; 20(3):282-96. PMC: 1361700. DOI: 10.1101/gad.1383206. View

16.

Lemon B, Inouye C, King D, Tjian R . Selectivity of chromatin-remodelling cofactors for ligand-activated transcription. Nature. 2002; 414(6866):924-8. DOI: 10.1038/414924a. View

17.

Kaileh M, Vanden Berghe W, Heyerick A, Horion J, Piette J, Libert C . Withaferin a strongly elicits IkappaB kinase beta hyperphosphorylation concomitant with potent inhibition of its kinase activity. J Biol Chem. 2006; 282(7):4253-4264. DOI: 10.1074/jbc.M606728200. View

18.

Lee G, Fields P, Griffin T, Flavell R . Regulation of the Th2 cytokine locus by a locus control region. Immunity. 2003; 19(1):145-53. DOI: 10.1016/s1074-7613(03)00179-1. View

19.

Duncliffe K, Bert A, Vadas M, Cockerill P . A T cell-specific enhancer in the interleukin-3 locus is activated cooperatively by Oct and NFAT elements within a DNase I-hypersensitive site. Immunity. 1997; 6(2):175-85. DOI: 10.1016/s1074-7613(00)80424-0. View

20.

Jani A, Wan M, Zhang J, Cui K, Wu J, Preston-Hurlburt P . A novel genetic strategy reveals unexpected roles of the Swi-Snf-like chromatin-remodeling BAF complex in thymocyte development. J Exp Med. 2008; 205(12):2813-25. PMC: 2585832. DOI: 10.1084/jem.20080938. View