STATs shape the active enhancer landscape of T cell populations
- PMID: 23178119
- PMCID: PMC3509201
- DOI: 10.1016/j.cell.2012.09.044
STATs shape the active enhancer landscape of T cell populations
Abstract
Signaling pathways are intimately involved in cellular differentiation, allowing cells to respond to their environment by regulating gene expression. Although enhancers are recognized as key elements that regulate selective gene expression, the interplay between signaling pathways and actively used enhancer elements is not clear. Here, we use CD4(+) T cells as a model of differentiation, mapping the activity of cell-type-specific enhancer elements in T helper 1 (Th1) and Th2 cells. Our data establish that STAT proteins have a major impact on the activation of lineage-specific enhancers and the suppression of enhancers associated with alternative cell fates. Transcriptome analysis further supports a functional role for enhancers regulated by STATs. Importantly, expression of lineage-defining master regulators in STAT-deficient cells fails to fully recover the chromatin signature of STAT-dependent enhancers. Thus, these findings point to a critical role of STATs as environmental sensors in dynamically molding the specialized enhancer architecture of differentiating cells.
Copyright © 2012 Elsevier Inc. All rights reserved.
Figures
![Figure 1](https://www.ncbi.nlm.nih.gov/pmc/articles/instance/3509201/bin/nihms419241f1.gif)
![Figure 2](https://www.ncbi.nlm.nih.gov/pmc/articles/instance/3509201/bin/nihms419241f2.gif)
![Figure 3](https://www.ncbi.nlm.nih.gov/pmc/articles/instance/3509201/bin/nihms419241f3.gif)
![Figure 4](https://www.ncbi.nlm.nih.gov/pmc/articles/instance/3509201/bin/nihms419241f4.gif)
![Figure 5](https://www.ncbi.nlm.nih.gov/pmc/articles/instance/3509201/bin/nihms419241f5.gif)
![Figure 6](https://www.ncbi.nlm.nih.gov/pmc/articles/instance/3509201/bin/nihms419241f6.gif)
Comment in
-
Designing an enhancer landscape.Cell. 2012 Nov 21;151(5):929-31. doi: 10.1016/j.cell.2012.11.007. Cell. 2012. PMID: 23178114 Free PMC article.
Similar articles
-
The polycomb protein Ezh2 regulates differentiation and plasticity of CD4(+) T helper type 1 and type 2 cells.Immunity. 2013 Nov 14;39(5):819-32. doi: 10.1016/j.immuni.2013.09.012. Immunity. 2013. PMID: 24238339
-
'All things considered': transcriptional regulation of T helper type 2 cell differentiation from precursor to effector activation.Immunology. 2013 Sep;140(1):31-8. doi: 10.1111/imm.12121. Immunology. 2013. PMID: 23668241 Free PMC article. Review.
-
Intestinal irradiation and fibrosis in a Th1-deficient environment.Int J Radiat Oncol Biol Phys. 2012 Sep 1;84(1):266-73. doi: 10.1016/j.ijrobp.2011.11.027. Epub 2012 Feb 13. Int J Radiat Oncol Biol Phys. 2012. PMID: 22336200
-
The transcription factors T-bet and GATA-3 control alternative pathways of T-cell differentiation through a shared set of target genes.Proc Natl Acad Sci U S A. 2009 Oct 20;106(42):17876-81. doi: 10.1073/pnas.0909357106. Epub 2009 Oct 5. Proc Natl Acad Sci U S A. 2009. PMID: 19805038 Free PMC article.
-
How are T(H)1 and T(H)2 effector cells made?Curr Opin Immunol. 2009 Apr;21(2):153-60. doi: 10.1016/j.coi.2009.03.010. Epub 2009 Apr 15. Curr Opin Immunol. 2009. PMID: 19375293 Free PMC article. Review.
Cited by
-
Allosterically activating SHP2 by oleanolic acid inhibits STAT3-Th17 axis for ameliorating colitis.Acta Pharm Sin B. 2024 Jun;14(6):2598-2612. doi: 10.1016/j.apsb.2024.03.017. Epub 2024 Mar 18. Acta Pharm Sin B. 2024. PMID: 38828149 Free PMC article.
-
A CTCF-binding site in the Mdm1-Il22-Ifng locus shapes cytokine expression profiles and plays a critical role in early Th1 cell fate specification.Immunity. 2024 May 14;57(5):1005-1018.e7. doi: 10.1016/j.immuni.2024.04.007. Epub 2024 May 1. Immunity. 2024. PMID: 38697116
-
NAB2-STAT6 drives an EGR1-dependent neuroendocrine program in Solitary Fibrous Tumors.bioRxiv [Preprint]. 2024 Apr 20:2024.04.15.589533. doi: 10.1101/2024.04.15.589533. bioRxiv. 2024. PMID: 38659891 Free PMC article. Preprint.
-
PU.1 and BCL11B sequentially cooperate with RUNX1 to anchor mSWI/SNF to poise the T cell effector landscape.Nat Immunol. 2024 May;25(5):860-872. doi: 10.1038/s41590-024-01807-y. Epub 2024 Apr 17. Nat Immunol. 2024. PMID: 38632339 Free PMC article.
-
Regulation of T helper cell differentiation by the interplay between histone modification and chromatin interaction.Immunity. 2024 May 14;57(5):987-1004.e5. doi: 10.1016/j.immuni.2024.03.018. Epub 2024 Apr 12. Immunity. 2024. PMID: 38614090
References
-
- Afkarian M, Sedy JR, Yang J, Jacobson NG, Cereb N, Yang SY, Murphy TL, Murphy KM. T-bet is a STATI-induced regulator for IL-12R expression in naive CD4+ T cells. Nature Immunology. 2002;3:549–557. - PubMed
-
- Ansel KM, Djuretic I, Tanasa B, Rao A. Regulation of Th2 differentiation and Il4 locus accessibility. Annual Review of Immunology. 2006;24:607–656. - PubMed
Publication types
MeSH terms
Substances
Associated data
- Actions
Grants and funding
LinkOut - more resources
Full Text Sources
Other Literature Sources
Research Materials