The POU-specific domain of Pit-1 is essential for sequence-specific, high affinity DNA binding and DNA-dependent Pit-1-Pit-1 interactions

Holly A. Ingraham, Sarah E. Flynn, Jeffrey W. Voss, Vivian R. Albert, Michael S. Kapiloff, Laura Wilson, Michael G. Rosenfeld

Research output: Contribution to journalArticlepeer-review

309 Scopus citations

Abstract

Pit-1 is a member of a family of transcription factors sharing two regions of homology: a highly conserved POU-specific (POUS) domain and a more divergent homeodomain (POUHD)- Analysis of mutant Pit-1 proteins suggests that, while the POUHD is required and sufficient for low affinity DNA binding, the POUS domain is necessary for high affinity binding and accurate recognition of natural Pit-1 response elements. Pit-1 is monomeric in solution but associates as a dimer on its DNA response element, exhibiting DNA-dependent protein-protein interactions requiring the POUS domain. Analysis of α-helical domains and conserved structures in Pit-1 suggests that POU domain proteins interact with their DNA recognition sites differently than classic homeodomain proteins, with both the POUHD and the POUS domain contacting DNA. Transcriptional activity of Pit-1 on enhancer elements is conferred primarily by a Ser- and Thr-rich N-terminal region unrelated to other known transcription-activating motifs.

Original languageEnglish (US)
Pages (from-to)1021-1033
Number of pages13
JournalCell
Volume61
Issue number6
DOIs
StatePublished - Jun 15 1990

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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