Journal
JOURNAL OF BIOLOGICAL CHEMISTRY
Volume 279, Issue 8, Pages 6576-6587Publisher
AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
DOI: 10.1074/jbc.M312270200
Keywords
-
Categories
Funding
- NCI NIH HHS [CA94170, CA81020, CA098301-01] Funding Source: Medline
Ask authors/readers for more resources
The breast- and ovarian-specific tumor suppressor BRCA1 has been implicated in both activation and repression of gene transcription by virtue of its direct interaction with sequence-specific DNA-binding transcription factors. However, the mechanistic basis by which BRCA1 mediates the transcriptional activity of these regulatory proteins remains largely unknown. To clarify this issue, we have examined the functional interaction between BRCA1 and ZBRK1, a BRCAl-dependent KRAB eight zinc finger transcriptional repressor. We report here the identification and molecular characterization of a portable BRCAl-dependent transcriptional repression domain within ZBRK1 composed of zinc fingers 5-8 along with sequences in the unique ZBRK1 C terminus. This C-terminal repression domain functions in a BRCAl-, histone deacetylase-, and promoter-specific manner and is thus functionally distinguishable from the N-terminal KRAB repression domain in ZBRK1, which exhibits no BRCA1 dependence and broad promoter specificity. Significantly, we also find that the BRCAl-dependent transcriptional repression domain on ZBRK1 includes elements that modulate its sequence-specific DNA binding activity. These findings thus reveal the presence within ZBRK1 of functionally bipartite zinc fingers with dual roles in sequence-specific DNA-binding and BRCAl-dependent transcriptional repression. We discuss the implications of these findings for the role of BRCA1 as ZBRK1 co-repressor.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available