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Epigenetic activation during Th17 cell differentiation is impaired after TRIM28 deletion

ABSTRACT: Cell fate decision is mediated by epigenetic mechanisms. We have analyzed naive T cell differentiation into Th17 cells, which is regulated by environmental cytokines and their downstream transcription factors. RORγt is a lineage-specific master transcription factor for Th17 cells. Although epigenetic mechanisms have been implicated in Th17 cell differentiation, how transcription factors interact to activate epigenetic program is unclear. Here we show that tripartite motif containing 28 (TRIM28) expression in Th17 cells is required for cytokine production and autoimmune diseases. Genome-wide occupancy analysis reveals that TRIM28 bound regions contain many super-enhancers, which are impaired after TRIM28 or STAT3 but not RORγt deletion. Importantly, TRIM28 exists in a complex with STAT3 and RORγt; TRIM28 recruitment to the Il17 gene requires STAT3, and further promotes RORγt recruitment. TRIM28 thus is a key player in the epigenetic activation during T cell differentiation.

ORGANISM(S): Mus musculus

PROVIDER: GSE108598 | GEO | 2018/02/28

REPOSITORIES: GEO

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Epigenetic activation during Th17 cell differentiation is impaired after TRIM28 deletion

Project description:Cell fate decision is mediated by epigenetic mechanisms. We have analyzed naive T cell differentiation into Th17 cells, which is regulated by environmental cytokines and their downstream transcription factors. RORγt is a lineage-specific master transcription factor for Th17 cells. Although epigenetic mechanisms have been implicated in Th17 cell differentiation, how transcription factors interact to activate epigenetic program is unclear. Here we show that tripartite motif containing 28 (TRIM28) expression in Th17 cells is required for cytokine production and autoimmune diseases. Genome-wide occupancy analysis reveals that TRIM28 bound regions contain many super-enhancers, which are impaired after TRIM28 or STAT3 but not RORγt deletion. Importantly, TRIM28 exists in a complex with STAT3 and RORγt; TRIM28 recruitment to the Il17 gene requires STAT3, and further promotes RORγt recruitment. TRIM28 thus is a key player in the epigenetic activation during T cell differentiation.

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Epigenetic activation during Th17 cell differentiation is impaired after TRIM28 deletion

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| PRJNA427793 | ENA