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TCF-1 promotes chromatin interactions across topologically associating domains in T cell progenitors.

ABSTRACT: The high mobility group (HMG) transcription factor TCF-1 is essential for early T cell development. Although in vitro biochemical assays suggest that HMG proteins can serve as architectural elements in the assembly of higher-order nuclear organization, the contribution of TCF-1 on the control of three-dimensional (3D) genome structures during T cell development remains unknown. Here, we investigated the role of TCF-1 in 3D genome reconfiguration. Using gain- and loss-of-function experiments, we discovered that the co-occupancy of TCF-1 and the architectural protein CTCF altered the structure of topologically associating domains in T cell progenitors, leading to interactions between previously insulated regulatory elements and target genes at late stages of T cell development. The TCF-1-dependent gain in long-range interactions was linked to deposition of active enhancer mark H3K27ac and recruitment of the cohesin-loading factor NIPBL at active enhancers. These data indicate that TCF-1 has a role in controlling global genome organization during T cell development.

SUBMITTER: Wang W

PROVIDER: S-EPMC9728953 | biostudies-literature | 2022 Jul

REPOSITORIES: biostudies-literature

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TCF-1 promotes chromatin interactions across topologically associating domains in T cell progenitors.

Wang Wenliang W Chandra Aditi A Goldman Naomi N Yoon Sora S Ferrari Emily K EK Nguyen Son C SC Joyce Eric F EF Vahedi Golnaz G

Nature immunology 20220620 7

The high mobility group (HMG) transcription factor TCF-1 is essential for early T cell development. Although in vitro biochemical assays suggest that HMG proteins can serve as architectural elements in the assembly of higher-order nuclear organization, the contribution of TCF-1 on the control of three-dimensional (3D) genome structures during T cell development remains unknown. Here, we investigated the role of TCF-1 in 3D genome reconfiguration. Using gain- and loss-of-function experiments, we ...[more]

PMID: 35726060

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Dataset Information

TCF-1 promotes chromatin interactions across topologically associating domains in T cell progenitors.

Publications

TCF-1 promotes chromatin interactions across topologically associating domains in T cell progenitors.

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