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Multiple mechanisms of transcriptional repression by YY1
1Department of Pathology, Harvard Cancer Center, Harvard Medical School, Boston, Massachusetts 02115, USA.
Abstract:
The four C-terminal GLI-Krüppel type zinc fingers of YY1 have been identified as a transcriptional repression domain. Previous reports have proposed DNA-bending and activator-quenching mechanisms for this zinc finger-mediated repression. In addition, previous work indicated that p300 and CBP might be involved in YY1-mediated repression. We have analyzed these possible models for the zinc finger-mediated repression. The role of each zinc finger in the repression and DNA-binding functions was determined by using a structure-and-function approach. We show that zinc finger 2 of YY1 plays a central role in both DNA binding and transcriptional repression. However, a survey of a panel of YY1 mutants indicates that these two functions can be separated, which argues against the DNA-bending model for repression. We show that the physical interaction between YY1 and p300, a coactivator for CREB, is not sufficient for repression of CREB-mediated transcription. Our studies indicate that YY1 functions as an activator-specific repressor. Repression of CTF-1-directed transcription may be accomplished through direct physical interaction between YY1 and this activator. In contrast, physical interaction is not necessary for YY1 to repress Sp1- and CREB-mediated transcription. Rather, the repression likely reflects an ability of YY1 to interfere with communication between these activators and their targets within the general transcription machinery. Taken together, our results suggest that YY1 employs multiple mechanisms to achieve activator-specific repression.
Insights
The transcription factor YY1 uses its zinc fingers to repress gene activity. Researchers found YY1 acts as an activator-specific repressor, employing multiple mechanisms to control transcription based on the target activator.
Area of Science:
- Molecular Biology
- Gene Regulation
- Transcription Factors
Background:
- The transcription factor YY1 (Yin Yang 1) possesses a C-terminal repression domain composed of four GLI-Krüppel type zinc fingers.
- Previous models proposed DNA-bending or activator-quenching as mechanisms for YY1-mediated repression, with potential involvement of p300 and CBP.
Purpose of the Study:
- To investigate the mechanisms of YY1-mediated transcriptional repression.
- To elucidate the specific roles of individual zinc fingers in YY1's DNA binding and repression functions.
- To determine if YY1 acts as a general repressor or an activator-specific repressor.
Main Methods:
- Structure-and-function analysis of YY1 mutants to assess DNA binding and repression.
- Investigation of the interaction between YY1 and coactivators like p300.
- Comparative analysis of YY1's repression of transcription directed by different activators (CTF-1, Sp1, CREB).
Main Results:
- Zinc finger 2 of YY1 is crucial for both DNA binding and transcriptional repression.
- The functions of DNA binding and repression by YY1 can be dissociated, arguing against a DNA-bending repression model.
- Physical interaction with p300 is insufficient for repressing CREB-mediated transcription.
- YY1 functions as an activator-specific repressor, utilizing distinct mechanisms for different activators.
Conclusions:
- YY1 employs multiple, activator-specific mechanisms for transcriptional repression.
- Repression of CTF-1 involves direct physical interaction with YY1.
- Repression of Sp1 and CREB likely occurs by YY1 interfering with activator communication to the general transcription machinery.