TI  - Multiple mechanisms of transcriptional repression by <prot>YY1</prot>.
PG  - 3723-32
AB  - The four C-terminal GLI-Kruppel type zinc fingers of <prot>YY1</prot> 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 <prot>p300</prot>
      and <prot>CBP</prot> might be involved in <prot>YY1</prot>-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 <prot>YY1</prot> plays a central role in both DNA binding and
      transcriptional repression. However, a survey of a panel of <prot>YY1</prot> 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  <prot>YY1</prot>  and  <prot>p300</prot> , a coactivator for <prot>CREB</prot>, is not
      sufficient for repression of <prot>CREB</prot>-mediated transcription. Our studies
      indicate that <prot>YY1</prot> functions as an activator-specific repressor. Repression
      of  <prot>CTF-1</prot> -directed transcription may be accomplished through direct
      physical interaction between  <prot>YY1</prot>  and this activator. In contrast, physical
      interaction is not necessary for <prot>YY1</prot> to repress <prot>Sp1</prot>- and <prot>CREB</prot>-mediated
      transcription. Rather, the repression likely reflects an ability of <prot>YY1</prot> to
      interfere with communication between these activators and their targets
      within the general transcription machinery. Taken together, our results
      suggest that <prot>YY1</prot> employs multiple mechanisms to achieve activator-specific
      repression.
AD  - Department of Pathology, Harvard Cancer Center, Harvard Medical School,
