Critical role of IRF1 and BATF in forming chromatin landscape during type 1 regulatory cell differentiation.
Type 1 regulatory T cells (Tr1 cells) are induced by interleukin-27 (IL-27) and have critical roles in the control of autoimmunity and resolution of inflammation. We found that the transcription factors IRF1 and BATF were induced early on after treatment with IL-27 and were required for the differentiation and function of Tr1 cells in vitro and in vivo. Epigenetic and transcriptional analyses revealed that both transcription factors influenced chromatin accessibility and expression of the genes required for Tr1 cell function. IRF1 and BATF deficiencies uniquely altered the chromatin landscape, suggesting that these factors serve a pioneering function during Tr1 cell differentiation.
Evergrande Center for Immunologic Diseases, Harvard Medical School and Brigham and Women's Hospital, Boston, Massachusetts, USA.
Katarzyna
K
Karwacz
Center for Computational Biology, Flatiron Institute, Simons Foundation, New York, New York, USA.|Skirball Institute for Biomolecular Medicine, New York University School of Medicine, New York, New York, USA.
Emily R
ER
Miraldi
Skirball Institute for Biomolecular Medicine, New York University School of Medicine, New York, New York, USA.
Maria
M
Pokrovskii
Evergrande Center for Immunologic Diseases, Harvard Medical School and Brigham and Women's Hospital, Boston, Massachusetts, USA.
Asaf
A
Madi
Department of Electrical Engineering and Computer Science and Center for Computational Biology, University of California, Berkeley, Berkeley, California, USA.
Nir
N
Yosef
Broad Institute of the Massachusetts Institute of Technology and Harvard University, Cambridge, Massachusetts, USA.
Ivo
I
Wortman
Department of Biology, New York University, New York, New York, USA.
Xi
X
Chen
Center for Computational Biology, Flatiron Institute, Simons Foundation, New York, New York, USA.
Aaron
A
Watters
Center for Computational Biology, Flatiron Institute, Simons Foundation, New York, New York, USA.
Nicholas
N
Carriero
Center for Human Microbial Ecology, Translational Health Science and Technology Institute (an autonomous institute of Department of Biotechnology, Govt. of India), NCR Biotech Science Cluster, Faridabad, India.
Amit
A
Awasthi
Broad Institute of the Massachusetts Institute of Technology and Harvard University, Cambridge, Massachusetts, USA.
Aviv
A
Regev
Center for Computational Biology, Flatiron Institute, Simons Foundation, New York, New York, USA.|Department of Biology, New York University, New York, New York, USA.
Richard
R
Bonneau
Skirball Institute for Biomolecular Medicine, New York University School of Medicine, New York, New York, USA.
Dan
D
Littman
Evergrande Center for Immunologic Diseases, Harvard Medical School and Brigham and Women's Hospital, Boston, Massachusetts, USA.
Vijay K
VK
Kuchroo
D000818:Animals; D001327:Autoimmune Diseases / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D015551:Autoimmunity; D050976:Basic-Leucine Zipper Transcription Factors / Q000235:genetics / Q000378:metabolism*; D002454:Cell Differentiation / Q000235:genetics / Q000276:immunology*; D002843:Chromatin / Q000235:genetics / Q000378:metabolism*; D016000:Cluster Analysis; D016207:Cytokines / Q000378:metabolism / Q000494:pharmacology; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D053263:Gene Regulatory Networks; D050856:Interferon Regulatory Factor-1 / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D011401:Promoter Regions, Genetic; D016176:T-Lymphocyte Subsets / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D050378:T-Lymphocytes, Regulatory / Q000166:cytology / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism*; D014157:Transcription Factors / Q000378:metabolism; D059467:Transcriptome
D050976:Basic-Leucine Zipper Transcription Factors; C431772:Batf protein, mouse; D002843:Chromatin; D016207:Cytokines; D050856:Interferon Regulatory Factor-1; D014157:Transcription Factors