Function of a Foxp3 cis-element in protecting regulatory T cell identity
Autor: | Yuqiong Liang, Xudong Li, Ye Zheng, Mathias Leblanc, Christopher Benner |
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Rok vydání: | 2014 |
Předmět: |
Encephalomyelitis
Autoimmune Experimental Regulatory T cell Cellular differentiation Molecular Sequence Data Gene Expression chemical and pharmacologic phenomena Biology Regulatory Sequences Nucleic Acid Editorials: Cell Cycle Features T-Lymphocytes Regulatory General Biochemistry Genetics and Molecular Biology Mice Immune system medicine Animals Transcription factor Conserved Sequence Genetics Base Sequence Biochemistry Genetics and Molecular Biology(all) T-cell receptor FOXP3 NFAT hemic and immune systems Cell Differentiation Forkhead Transcription Factors Lymphoproliferative Disorders Cell biology medicine.anatomical_structure Regulatory sequence CpG Islands |
Zdroj: | Cell. 158(4) |
ISSN: | 1097-4172 |
Popis: | SummaryThe homeostasis of multicellular organisms requires terminally differentiated cells to preserve their lineage specificity. However, it is unclear whether mechanisms exist to actively protect cell identity in response to environmental cues that confer functional plasticity. Regulatory T (Treg) cells, specified by the transcription factor Foxp3, are indispensable for immune system homeostasis. Here, we report that conserved noncoding sequence 2 (CNS2), a CpG-rich Foxp3 intronic cis-element specifically demethylated in mature Tregs, helps maintain immune homeostasis and limit autoimmune disease development by protecting Treg identity in response to signals that shape mature Treg functions and drive their initial differentiation. In activated Tregs, CNS2 helps protect Foxp3 expression from destabilizing cytokine conditions by sensing TCR/NFAT activation, which facilitates the interaction between CNS2 and Foxp3 promoter. Thus, epigenetically marked cis-elements can protect cell identity by sensing key environmental cues central to both cell identity formation and functional plasticity without interfering with initial cell differentiation. |
Databáze: | OpenAIRE |
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