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OCA-T1 and OCA-T2 are coactivators of POU2F3 in the tuft cell lineage

ABSTRACT: ChIP-Seq of C11orf53(OCA-T), COLCA2 and POU2F3(OCT11) in tuft cell lung cancer cell lines. Gene expression changes upon CRISPR knockout of different genes in tuft cell lung cancer cell lines and upon over-expression of C11orf53/POU2F3 alone or in combo in YT330 (a murine Notch high small cell lung cancer cell line)

ORGANISM(S): Mus musculus Homo sapiens

PROVIDER: GSE186614 | GEO | 2022/05/01

REPOSITORIES: GEO

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OCA-T1 and OCA-T2 are coactivators of POU2F3 in the tuft cell lineage

Project description:OCA-T1 and OCA-T2 are coactivators of POU2F3 in the tuft cell lineage

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POU2AF2/C11orf53 functions as a co-activator of POU2F3 by maintaining chromatin accessibility and enhancer activity

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A SWI/SNF-dependent transcriptional repression mediated by POU2AF2/C11orf53 at enhancer.

Project description:Recent studies have identified a previously uncharacterized protein C11orf53 (now named POU2AF2/OCA-T1), functions as a new co-activator of POU2F3, the master transcription factor which is critical for both normal and neoplastic tuft cell identity and viability. Here, we demonstrated that POU2AF2 functions as an “Yin-Yang” factor which mediates both transcriptional activation and repression at distal enhance elements. The proteomics study aims to identify potential interactors with POU2AF2 in different cell lines which may enable us to further understand the function of POU2AF2 in human cancer.

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Mammalian SWI/SNF complex activity regulates POU2F3 and constitutes a targetable dependency in small cell lung cancer

Project description:Small cell lung cancers (SCLC) are comprised of heterogeneous subtypes marked by lineage-specific transcription factors, including ASCL1, NEUROD1, and POU2F3. POU2F3-positive SCLC, ~12% of all cases, are uniquely dependent on POU2F3 itself; as such, approaches to attenuate POU2F3 expression may represent new therapeutic opportunities for this subtype. Here using genome-scale CRISPR/Cas9-based screens reporting on POU2F3 expression in SCLC cell lines, we define mSWI/SNF complexes, including non-canonical BAF complexes (ncBAF), as top regulators of POU2F3 and dependencies specific to the POU2F3-positive subtype. Notably, clinical-grade pharmacologic mSWI/SNF complex inhibition attenuates proliferation of all POU2F3-positive SCLCs, while disruption of ncBAF via BRD9 degradation is uniquely effective in pure non-neuroendocrine POU2F3-SCLCs. mSWI/SNF complexes maintain accessibility over gene loci central to POU2F3-mediated gene regulatory networks. Finally, chemical targeting of SMARCA4/2 mSWI/SNF ATPases and BRD9 decrease POU2F3-SCLC tumor growth and increase survival in vivo. Taken together, these results define mSWI/SNF-mediated global governance of the POU2F3 oncogenic program and suggest mSWI/SNF inhibition as a therapeutic strategy in SCLC.

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Project description:POU2F3 is a master regulator of a tuft cell-like variant of small cell lung cancer [ChIP-seq]

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Project description:POU2F3 is a master regulator of a tuft cell-like variant of small cell lung cancer [RNA-seq]

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