Structural insights into a highly flexible zinc finger module unravel INSM1 function in transcription regulation.

ABSTRACT: Orderly development of neuroendocrine and nervous system of mammals requires INSM1, a key regulator for cell differentiation. Ectopic expression of INSM1 is closely correlated with human neuroendocrine tumorigenesis, which makes INSM1 a reliable diagnostic biomarker and potential therapeutic target. To date, INSM1 is known as a transcription repressor binding to GGGG-contained DNA element and TEAD1 using its five zinc fingers (ZFs), while the binding mechanism remains unknown. Here, we reveal highly variable conformations of the whole structure of the five ZFs, among which ZF1 adopts an unusual CCHC-fold. ZF1 binds to the TEAD domain of TEAD1 through hydrophobic interactions, and forms a ternary complex with TEAD1 and TEAD1-targeted DNA. Based on this, INSM1 cooperates with TEAD1 to repres

SUBMITTER: Zhou H 

PROVIDER: S-EPMC11880201 | biostudies-literature | 2025 Mar

REPOSITORIES: biostudies-literature