Sequence-specific transcriptional corepressor function for BRCA1 through a novel zinc finger protein, ZBRK1

Lei Zheng; Hongyi Pan; Shang Li; Andrea Flesken-Nikitin; Phang Lang Chen; Thomas G. Boyer; Wen Hwa Lee

doi:10.1016/S1097-2765(00)00075-7

Sequence-specific transcriptional corepressor function for BRCA1 through a novel zinc finger protein, ZBRK1

Lei Zheng, Hongyi Pan, Shang Li, Andrea Flesken-Nikitin, Phang Lang Chen, Thomas G. Boyer, Wen Hwa Lee

Department of Molecular Medicine

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

205 Scopus citations

Abstract

BRCA1 has been implicated in the transcriptional regulation of DNA damage-inducible genes that function in cell cycle arrest. To explore the mechanistic basis for this regulation, a novel human gene, ZBRK1, which encodes a 60 kDa protein with an N-terminal KRAB domain and eight central zinc fingers, was identified by virtue of its interaction with BRCA1 in vitro and in vivo. ZBRK1 binds to a specific sequence, GGGxxx CAGxxxTTT, within GADD45 intron 3 that supports the assembly of a nuclear complex minimally containing both ZBRK1 and BRCA1. ZBRK1 represses transcription through this recognition sequence in a BRCA1-dependent manner. These results thus reveal a novel corepressor function for BRCA1 and provide a mechanistic basis for the biological activity of BRCA1 through sequence-specific transcriptional regulation.

Original language	English (US)
Pages (from-to)	757-768
Number of pages	12
Journal	Molecular Cell
Volume	6
Issue number	4
DOIs	https://doi.org/10.1016/S1097-2765(00)00075-7
State	Published - 2000

ASJC Scopus subject areas

Molecular Biology
Cell Biology

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@article{73b97723938e45408a05bd023cb48ad7,

title = "Sequence-specific transcriptional corepressor function for BRCA1 through a novel zinc finger protein, ZBRK1",

abstract = "BRCA1 has been implicated in the transcriptional regulation of DNA damage-inducible genes that function in cell cycle arrest. To explore the mechanistic basis for this regulation, a novel human gene, ZBRK1, which encodes a 60 kDa protein with an N-terminal KRAB domain and eight central zinc fingers, was identified by virtue of its interaction with BRCA1 in vitro and in vivo. ZBRK1 binds to a specific sequence, GGGxxx CAGxxxTTT, within GADD45 intron 3 that supports the assembly of a nuclear complex minimally containing both ZBRK1 and BRCA1. ZBRK1 represses transcription through this recognition sequence in a BRCA1-dependent manner. These results thus reveal a novel corepressor function for BRCA1 and provide a mechanistic basis for the biological activity of BRCA1 through sequence-specific transcriptional regulation.",

author = "Lei Zheng and Hongyi Pan and Shang Li and Andrea Flesken-Nikitin and Chen, {Phang Lang} and Boyer, {Thomas G.} and Lee, {Wen Hwa}",

note = "Funding Information: The first two authors contributed equally to this paper. We thank Dr. D.A. Haber and Dr. A.J. Fornace, Jr. for their generosity in providing plasmids. We thank Dr. Z.D. Sharp and Dr. N. Ting for critical comments, and C.-F. Chen, D. Jones, and P. Garza for technical assistance in plasmid construction and antibody preparation. This work was supported by National Institutes of Health grants and McDermott endowment funds to W.-H. L.; L. Z. and S. L. were supported by a predoctoral training grant from the U.S. Army (DAMD17-99-1-9402). ",

year = "2000",

doi = "10.1016/S1097-2765(00)00075-7",

language = "English (US)",

volume = "6",

pages = "757--768",

journal = "Molecular Cell",

issn = "1097-2765",

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T1 - Sequence-specific transcriptional corepressor function for BRCA1 through a novel zinc finger protein, ZBRK1

AU - Zheng, Lei

AU - Pan, Hongyi

AU - Li, Shang

AU - Flesken-Nikitin, Andrea

AU - Chen, Phang Lang

AU - Boyer, Thomas G.

AU - Lee, Wen Hwa

N1 - Funding Information: The first two authors contributed equally to this paper. We thank Dr. D.A. Haber and Dr. A.J. Fornace, Jr. for their generosity in providing plasmids. We thank Dr. Z.D. Sharp and Dr. N. Ting for critical comments, and C.-F. Chen, D. Jones, and P. Garza for technical assistance in plasmid construction and antibody preparation. This work was supported by National Institutes of Health grants and McDermott endowment funds to W.-H. L.; L. Z. and S. L. were supported by a predoctoral training grant from the U.S. Army (DAMD17-99-1-9402).

PY - 2000

Y1 - 2000

N2 - BRCA1 has been implicated in the transcriptional regulation of DNA damage-inducible genes that function in cell cycle arrest. To explore the mechanistic basis for this regulation, a novel human gene, ZBRK1, which encodes a 60 kDa protein with an N-terminal KRAB domain and eight central zinc fingers, was identified by virtue of its interaction with BRCA1 in vitro and in vivo. ZBRK1 binds to a specific sequence, GGGxxx CAGxxxTTT, within GADD45 intron 3 that supports the assembly of a nuclear complex minimally containing both ZBRK1 and BRCA1. ZBRK1 represses transcription through this recognition sequence in a BRCA1-dependent manner. These results thus reveal a novel corepressor function for BRCA1 and provide a mechanistic basis for the biological activity of BRCA1 through sequence-specific transcriptional regulation.

AB - BRCA1 has been implicated in the transcriptional regulation of DNA damage-inducible genes that function in cell cycle arrest. To explore the mechanistic basis for this regulation, a novel human gene, ZBRK1, which encodes a 60 kDa protein with an N-terminal KRAB domain and eight central zinc fingers, was identified by virtue of its interaction with BRCA1 in vitro and in vivo. ZBRK1 binds to a specific sequence, GGGxxx CAGxxxTTT, within GADD45 intron 3 that supports the assembly of a nuclear complex minimally containing both ZBRK1 and BRCA1. ZBRK1 represses transcription through this recognition sequence in a BRCA1-dependent manner. These results thus reveal a novel corepressor function for BRCA1 and provide a mechanistic basis for the biological activity of BRCA1 through sequence-specific transcriptional regulation.

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Sequence-specific transcriptional corepressor function for BRCA1 through a novel zinc finger protein, ZBRK1

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