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FoxP3 associates with enhancer-promoter loops to regulate Treg-specific gene expression [HiChIP]

ABSTRACT: We applied proximity-ligation with chromatin immunoprecipitation (HiChIP) in Treg and closely related conventional CD4+ T cells (Tconv) to map the H3K27Ac, FoxP3 and Yy1 chromatin structures.

ORGANISM(S): Mus musculus

PROVIDER: GSE189442 | GEO | 2021/11/26

REPOSITORIES: GEO

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FoxP3 associates with enhancer-promoter loops to regulate Treg-specific gene expression [HiChIP]

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Project description:There is considerable evidence that chromosome structure plays important roles in gene control, but we have limited understanding of the proteins that contribute to structural interactions between gene promoters and their enhancer elements. Large DNA loops that encompass genes and their regulatory elements depend on CTCF-CTCF interactions, but most enhancer-promoter interactions do not depend on this structural protein. Here we show that the transcription factor Yin Yang 1 (YY1) contributes to enhancer-promoter structural interactions in a manner analogous to DNA interactions mediated by CTCF. YY1 binds to active enhancers and promoter-proximal elements in all cells examined. YY1 forms dimers that can facilitate DNA interactions. Deletion of YY1 binding sites or depletion of YY1 can disrupt enhancer-promoter looping and normal gene expression. We propose that YY1-mediated enhancer-promoter interactions are a general feature of mammalian gene control.

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FoxP3 associates with enhancer-promoter loops to regulate Treg-specific gene expression

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Pre-established chromatin interactions mediate acute transcriptional response to Epo [HiChIP]

Project description:Although chromatin architecture has been established in a variety of cell and tissue types, chromatin contacts’ dynamics in response to hormone stimulation has yet to be fully elucidated. Using the unique anemia-inducing strain of the Friend virus (FVA) murine model system, we show that there are transcriptional and epigenetic changes in response to erythropoietin within an invariant chromatin domain organization. There is an acute transcriptional response, as seen by genes with significant differential RNA polymerase II occupancy. Additionally, we find that YY1 is highly dynamic in response to Epo stimulation and these binding locations are not shared with CTCF. Using HiChIP, which combines Hi-C and ChIP methodologies, we identified enhancer-promoter interactions mediated by H3K27ac and YY1, revealing a subset of invariant chromatin loops. Together, these findings offer new insights into Epo-mediated gene regulation through chromatin organization.

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Role of interleukin 2 on thymic Foxp3+CD4+ regulatory T (Treg) cell chromatin modeling

Project description:Interleukine 2 (IL-2) is still one of the most interesting cytokines in T cell biology with its ability to control immune homeostasis by maintaining the functional identity of Foxp3+ regulatory T (Treg) cells and the expansion of activated conventional T (Tconv) cells. Yet, how IL-2 exactly enables Treg cells to suppress autoreactive Tconv cells and to maintain their identity is unclear. Using a mouse model in which IL-2 signaling via its high affinity receptor CD25 is selectively impaired, the “Il2ramut/mut” mouse, we report that Treg cells that only receive low IL-2 signals keep Il2ramut/mut but not WT Tconv cells “in check”, suggesting equal IL-2 signals in Treg and Tconv cells is essential to safeguard immune homeostasis. Furthermore, the comparative analysis of gene expression and epigenetic landscape of Il2ramut/mut and WT Treg cells support a model in which IL-2 "locks in” Treg cell identity and functions in vivo by controlling their genome-wide chromatin accessibility.

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Project description:H3K27ac HiChIP analysis was performed in an B-ALL cell line to analyze active chromatin-chromatin interactions in B-ALL cells.

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