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PU.1 and BCL11B sequentially cooperate with RUNX1 to anchor mSWI/SNF to poise the T cell effector landscape [CUT&RUN]

ABSTRACT: T cells trigger non-specific signaling pathways to elicit specialized effector functions to eliminate pathogens and cancers. Chromatin accessibility at T effector loci prior to antigen encounter poises cells to couple antigen recognition to the activation of lineage-specific responses. Here, by tracing the chromatin accessibility profiles unique to T effector functions during development, we find that the majority of T effector loci become accessible prior to antigen receptor expression. Epigenomic feature analysis, biochemical studies, and inducible perturbations identified two mechanistic linchpins: the physical association of the mSWI/SNF remodeling complex to the pleiotropic transcription factor (TF) RUNX1, and the cooperativity between RUNX1 and lineage-defining TFs PU.1 and BCL11B that respectively facilitate the establishment and maintenance of chromatin accessibility at T effector loci in early thymocyte progenitors. These findings reflect a design principle that allows distinct cell types to use the same signaling pathways to execute disparate roles which collectively orchestrate the immune response.

ORGANISM(S): Mus musculus

PROVIDER: GSE234330 | GEO | 2023/06/08

REPOSITORIES: GEO

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PU.1 and BCL11B sequentially cooperate with RUNX1 to anchor mSWI/SNF to poise the T cell effector landscape [RNA-seq]

Project description:T cells trigger non-specific signaling pathways to elicit specialized effector functions to eliminate pathogens and cancers. Chromatin accessibility at T effector loci prior to antigen encounter poises cells to couple antigen recognition to the activation of lineage-specific responses. Here, by tracing the chromatin accessibility profiles unique to T effector functions during development, we find that the majority of T effector loci become accessible prior to antigen receptor expression. Epigenomic feature analysis, biochemical studies, and inducible perturbations identified two mechanistic linchpins: the physical association of the mSWI/SNF remodeling complex to the pleiotropic transcription factor (TF) RUNX1, and the cooperativity between RUNX1 and lineage-defining TFs PU.1 and BCL11B that respectively facilitate the establishment and maintenance of chromatin accessibility at T effector loci in early thymocyte progenitors. These findings reflect a design principle that allows distinct cell types to use the same signaling pathways to execute disparate roles which collectively orchestrate the immune response.

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