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

317 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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10.1016/0092-8674(90)90067-O

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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.",

author = "Ingraham, {Holly A.} and Flynn, {Sarah E.} and Voss, {Jeffrey W.} and Albert, {Vivian R.} and Kapiloff, {Michael S.} and Laura Wilson and Rosenfeld, {Michael G.}",

note = "Funding Information: We are especially grateful to Drs. Christopher Glass and Stuart Adler for useful discussions and experimental advice. We thank Dan Drolet, Xi He, and Maurice Treaty for careful review of the manuscript and Chuck Nelson for maintenance and aid in tissue culture experiments. These studies were supported by a grant from the National Institute of Arthritis, Diabetes, and Digestive and Kidney Diseases. M. G. R. is an Investigator with the Howard Hughes Medical Institute. J. W. V. is an American Cancer Society fellow.",

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AU - Wilson, Laura

AU - Rosenfeld, Michael G.

N1 - Funding Information: We are especially grateful to Drs. Christopher Glass and Stuart Adler for useful discussions and experimental advice. We thank Dan Drolet, Xi He, and Maurice Treaty for careful review of the manuscript and Chuck Nelson for maintenance and aid in tissue culture experiments. These studies were supported by a grant from the National Institute of Arthritis, Diabetes, and Digestive and Kidney Diseases. M. G. R. is an Investigator with the Howard Hughes Medical Institute. J. W. V. is an American Cancer Society fellow.

PY - 1990/6/15

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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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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

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