Multitasking C2H2 zinc fingers link Zac DNA binding to coordinated regulation of p300-histone acetyltransferase activity.
Zac is a C(2)H(2) zinc finger protein that regulates apoptosis and cell cycle arrest through DNA binding and transactivation. The coactivator proteins p300/CBP enhance transactivation through their histone acetyltransferase (HAT) activity by modulating chromatin structure. Here, we show that p300 increases Zac transactivation in a strictly HAT-dependent manner. Whereas the classic recruitment model proposes that coactivation simply depends on the capacity of the activator to recruit the coactivator, we demonstrate that coordinated binding of Zac zinc fingers and C terminus to p300 regulates HAT function by increasing histone and acetyl coenzyme A affinities and catalytic activity. This concerted regulation of HAT function is mediated via the KIX and CH3 domains of p300 in an interdependent manner. Interestingly, Zac zinc fingers 6 and 7 simultaneously play key roles in DNA binding and p300 regulation. Our findings demonstrate, for the first time, that C(2)H(2) zinc fingers can link DNA binding to HAT signaling and suggest a dynamic role for DNA-binding proteins in the enzymatic control of transcription.
Hoffmann
Anke
A
Molecular Neuroendocrinology, Max Planck Institute of Psychiatry, Kraepelinstrasse 2-10, D-80804 Munich, Germany.
Barz
Thomas
T
Spengler
Dietmar
D
D000818:Animals; D001483:Base Sequence; D001665:Binding Sites; D018797:Cell Cycle Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D004247:DNA / Q000235:genetics / Q000378:metabolism*; D050881:E1A-Associated p300 Protein / Q000378:metabolism*; D006367:HeLa Cells; D051548:Histone Acetyltransferases / Q000378:metabolism*; D006801:Humans; D007700:Kinetics; D018374:LLC-PK1 Cells; D046911:Macromolecular Substances; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D013552:Swine; D014157:Transcription Factors / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D015533:Transcriptional Activation; D025521:Tumor Suppressor Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D016335:Zinc Fingers
D018797:Cell Cycle Proteins; D046911:Macromolecular Substances; C106464:PLAGL1 protein, human; D014157:Transcription Factors; D025521:Tumor Suppressor Proteins; D004247:DNA; D050881:E1A-Associated p300 Protein; C494360:EP300 protein, human; D051548:Histone Acetyltransferases