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

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

PROVIDER: PRJNA473830 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR7236730.fastq.gz	Fastqsanger.gz
	SRR7236740.fastq.gz	Fastqsanger.gz
	SRR7236750.fastq.gz	Fastqsanger.gz
	SRR7236760.fastq.gz	Fastqsanger.gz
	SRR7236770.fastq.gz	Fastqsanger.gz

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POU2F3 is a master regulator of a tuft cell-like variant of small cell lung cancer

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

| PRJNA473826 | ENA

Structural Basis of DNA-Dependent Coactivator Recruitment by the Tuft Cell Master Regulator POU2F3 [DMS_Screen]

Project description:The transcription factor POU2F3 defines the identity of tuft cells and underlies a distinct molecular subtype of small cell lung cancer (SCLC). Although POU2F3 is considered undruggable, its activity critically depends on the coactivators OCA-T1 and OCA-T2. Here, we demonstrate that acute suppression of either POU2F3 or OCA-T1 induces regression of tuft cell-like SCLC xenografts in vivo. To explore the structural basis and druggability of this dependency, we solved crystal structures of POU2F3 bound to OCA-T1 or OCA-T2 in complex with DNA, revealing a tripartite, DNA-dependent interface. We further employed deep mutational scanning to systematically assess the functional impact of 4,218 missense variants in POU2F3 and OCA-T1, uncovering both mutation-sensitive hotspots and structurally constrained regions critical for tumor cell fitness. These findings define a unique transcriptional complex that integrates DNA recognition with coactivator recruitment and nominate POU2F3–OCA-T as a structurally tractable vulnerability in tuft cell-like carcinomas.

2026-01-01 | GSE302004 | GEO

Structural Basis of DNA-Dependent Coactivator Recruitment by the Tuft Cell Master Regulator POU2F3 [RNA-seq]

2026-01-01 | GSE302002 | GEO

Structural Basis of DNA-Dependent Coactivator Recruitment by the Tuft Cell Master Regulator POU2F3 [CUT&Run]

2026-01-01 | GSE302003 | GEO

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

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

| PRJNA473832 | ENA

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

Project description: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)

2022-05-01 | GSE186614 | GEO

Structural Basis of DNA-Dependent Coactivator Recruitment by the Tuft Cell Master Regulator POU2F3 [DMS_Screen]

Project description:Structural Basis of DNA-Dependent Coactivator Recruitment by the Tuft Cell Master Regulator POU2F3 [DMS_Screen]

| PRJNA1288269 | ENA

Structural Basis of DNA-Dependent Coactivator Recruitment by the Tuft Cell Master Regulator POU2F3 [CUT&Run]

Project description:Structural Basis of DNA-Dependent Coactivator Recruitment by the Tuft Cell Master Regulator POU2F3 [CUT&Run]

| PRJNA1288268 | ENA

Structural Basis of DNA-Dependent Coactivator Recruitment by the Tuft Cell Master Regulator POU2F3 [RNA-seq]

Project description:Structural Basis of DNA-Dependent Coactivator Recruitment by the Tuft Cell Master Regulator POU2F3 [RNA-seq]

| PRJNA1288267 | ENA

POU2F3 is a master regulator of a tuft cell-like variant of small cell lung cancer.

Project description:Small cell lung cancer (SCLC) is widely considered to be a tumor of pulmonary neuroendocrine cells; however, a variant form of this disease has been described that lacks neuroendocrine features. Here, we applied domain-focused CRISPR screening to human cancer cell lines to identify the transcription factor (TF) POU2F3 (POU class 2 homeobox 3; also known as SKN-1a/OCT-11) as a powerful dependency in a subset of SCLC lines. An analysis of human SCLC specimens revealed that POU2F3 is expressed exclusively in variant SCLC tumors that lack expression of neuroendocrine markers and instead express markers of a chemosensory lineage known as tuft cells. Using chromatin- and RNA-profiling experiments, we provide evidence that POU2F3 is a master regulator of tuft cell identity in a variant form of SCLC. Moreover, we show that most SCLC tumors can be classified into one of three lineages based on the expression of POU2F3, ASCL1, or NEUROD1. Our CRISPR screens exposed other unique dependencies in POU2F3-expressing SCLC lines, including the lineage TFs SOX9 and ASCL2 and the receptor tyrosine kinase IGF1R (insulin-like growth factor 1 receptor). These data reveal POU2F3 as a cell identity determinant and a dependency in a tuft cell-like variant of SCLC, which may reflect a previously unrecognized cell of origin or a trans-differentiation event in this disease.

| S-EPMC6075037 | biostudies-literature

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