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

doi:10.1016/0092-8674(90)90067-O

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

Pediatrics

Research output: Contribution to journal › Article › peer-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 (POU_S) domain and a more divergent homeodomain (POU_HD)- Analysis of mutant Pit-1 proteins suggests that, while the POU_HD is required and sufficient for low affinity DNA binding, the POU_S 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 POU_S 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 POU_HD and the POU_S 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 language	English (US)
Pages (from-to)	1021-1033
Number of pages	13
Journal	Cell
Volume	61
Issue number	6
DOIs	https://doi.org/10.1016/0092-8674(90)90067-O
State	Published - Jun 15 1990

ASJC Scopus subject areas

Biochemistry, Genetics and Molecular Biology(all)

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The POU-specific domain of Pit-1 is essential for sequence-specific, high affinity DNA binding and DNA-dependent Pit-1-Pit-1 interactions. / Ingraham, Holly A.; Flynn, Sarah E.; Voss, Jeffrey W.; Albert, Vivian R.; Kapiloff, Michael S.; Wilson, Laura; Rosenfeld, Michael G.

In: Cell, Vol. 61, No. 6, 15.06.1990, p. 1021-1033.

Research output: Contribution to journal › Article › peer-review

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

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.",

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AU - Voss, Jeffrey W.

AU - Albert, Vivian R.

AU - Kapiloff, Michael S.

AU - Wilson, Laura

AU - Rosenfeld, Michael G.

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N2 - 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.

AB - 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.

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