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SATB1 Regulates 3D Genome Architecture in T cells by Constraining Chromatin Interactions surrounding CTCF-binding sites [Hi-C]

ABSTRACT: SATB1, a nuclear matrix-associated protein, has long been proposed to function as a global chromatin loop organizer in T cells. However, the precise roles of SATB1 in chromatin organization remain elusive. Here we show that the depletion of SATB1 in immortalized T cells led to pronounced changes in gene expression, particularly for genes involved in cell proliferation and T cell activation, as well as 3D genome architecture at multiple scales, including the A/B compartment, topologically associating domains (TADs), and loops. Importantly, SATB1 extensively colocalizes with CTCF throughout the genome. Depletion of SATB1 led to increased association among the SATB1/CTCF co-occupied sites, as well as increased chromatin contacts across these sites, thereby altering the genome-wide chromatin loop landscape. SATB1 does not regulate genome architecture by modulating CTCF occupancy. Rather, the topological effects imposed by SATB1 may be attributed to SATB1-dependent anchoring of CTCF to the salt extraction-resistant nuclear matrix. Together, our findings suggest that the functional interplay between nuclear matrix and CTCF plays a critical role in orchestrating 3D genome organization.

ORGANISM(S): Homo sapiens

PROVIDER: GSE198259 | GEO | 2023/03/05

REPOSITORIES: GEO

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SATB1 Regulates 3D Genome Architecture in T cells by Constraining Chromatin Interactions surrounding CTCF-binding sites

Project description:SATB1, a nuclear matrix-associated protein, has long been proposed to function as a global chromatin loop organizer in T cells. However, the precise roles of SATB1 in chromatin organization remain elusive. Here we show that the depletion of SATB1 in immortalized T cells led to pronounced changes in gene expression, particularly for genes involved in cell proliferation and T cell activation, as well as 3D genome architecture at multiple scales, including the A/B compartment, topologically associating domains (TADs), and loops. Importantly, SATB1 extensively colocalizes with CTCF throughout the genome. Depletion of SATB1 led to increased association among the SATB1/CTCF co-occupied sites, as well as increased chromatin contacts across these sites, thereby altering the genome-wide chromatin loop landscape. SATB1 does not regulate genome architecture by modulating CTCF occupancy. Rather, the topological effects imposed by SATB1 may be attributed to SATB1-dependent anchoring of CTCF to the salt extraction-resistant nuclear matrix. Together, our findings suggest that the functional interplay between nuclear matrix and CTCF plays a critical role in orchestrating 3D genome organization.

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SATB1 Regulates 3D Genome Architecture in T cells by Constraining Chromatin Interactions surrounding CTCF-binding sites

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Project description:Spatial genome organization is critical for precise gene regulation during development. Special AT-rich sequence binding protein 1 (SATB1) has long been proposed to act as a global chromatin loop organizer in T cells. However, the exact functions of SATB1 in genome organization remain elusive. Here we show that the depletion of SATB1 in human and murine T cells led to transcriptional dysregulation for genes involved in T cell activation, as well as alterations of 3D genome architecture at multiple scales, including the A/B compartment, topologically associating domains (TADs), and loops. Importantly, SATB1 extensively colocalizes with CTCF throughout the genome. Depletion of SATB1 led to increased chromatin contacts among and across the SATB1/CTCF co-occupied sites, thereby affecting the transcription of critical genes involved in T cell activation. The loss of SATB1 did not affect the genome-wide occupancy of CTCF, but significantly reduced the retention of CTCF in the nuclear matrix. Collectively, our data reveal that SATB1 constrains chromatin topology surrounding CTCF-binding sites by tethering CTCF to the nuclear matrix, and suggest that the functional interplay between SATB1 and CTCF contributes to 3D genome organization.

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The nuclear matrix associating protein HNRNPU functions as a key regulator of 3D genome architecture [ChIP-Seq 2]

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SATB1 Regulates 3D Genome Architecture in T cells by Constraining Chromatin Interactions surrounding CTCF-binding sites

Project description:SATB1 Regulates 3D Genome Architecture in T cells by Constraining Chromatin Interactions surrounding CTCF-binding sites

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SATB1 Regulates 3D Genome Architecture in T cells by Constraining Chromatin Interactions surrounding CTCF-binding sites

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