POU2AF2/C11orf53 functions as a coactivator of POU2F3 by maintaining chromatin accessibility and enhancer activity

Small cell lung cancer (SCLC), accounting for around 13% of all lung cancers, often results in rapid tumor growth, early metastasis, and acquired therapeutic resistance. The POU class 2 homeobox 3 (POU2F3) is a master regulator of tuft cell identity and defines the SCLC-P subtype that lacks the neuroendocrine markers. Here, we have identi-fied a previously uncharacterized protein, C11orf53, which is coexpressed with POU2F3 in both SCLC cell lines and patient samples. Mechanistically, C11orf53 directly interacts with POU2F3 and is recruited to chromatin by POU2F3. Depletion of C11orf53 reduced enhancer H3K27ac levels and chromatin accessibility, resulting in a re-duction of POU2F3-dependent gene expression. On the basis of the molecular function of C11orf53, we renamed it as POU Class 2 Homeobox Associating Factor 2 (POU2AF2). In summary, our study has identified a new coact-ivator of POU2F3 and sheds light on the therapeutic potential of targeting POU2AF2/POU2F3 heterodimer in hu-man SCLC.

Automated summary

A previously unidentified protein, C11orf53, coexpressed with POU2F3, has been identified as a potential therapeutic target for small cell lung cancer (SCLC).