A new coactivator function for Zac1's C2H2 zinc finger DNA-binding domain in selectively controlling PCAF activity.
The generally accepted paradigm of transcription by regulated recruitment defines sequence-specific transcription factors and coactivators as separate categories that are distinguished by their abilities to bind DNA autonomously. The C(2)H(2) zinc finger protein Zac1, with an established role in canonical DNA binding, also acts as a coactivator. Commensurate with this function, p73, which is related to p53, is here shown to recruit Zac1, together with the coactivators p300 and PCAF, to the p21(Cip1) promoter during the differentiation of embryonic stem cells into neurons. In the absence of autonomous DNA binding, Zac1's zinc fingers stabilize the association of PCAF with p300, suggesting its scaffolding function. Furthermore, Zac1 regulates the affinities of PCAF substrates as well as the catalytic activities of PCAF to induce a selective switch in favor of histone H4 acetylation and thereby the efficient transcription of p21(Cip1). These results are consistent with an authentic coactivator function of Zac1's C(2)H(2) zinc finger DNA-binding domain and suggest coactivation by sequence-specific transcription factors as a new facet of transcriptional control.
Hoffmann
Anke
A
Molecular Neuroendocrinology, Max Planck Institute of Psychiatry, Kraepelinstr. 2-10, D-80804 Munich, Germany.
Spengler
Dietmar
D
D018797:Cell Cycle Proteins / Q000737:chemistry* / Q000378:metabolism*; D002454:Cell Differentiation; D045744:Cell Line, Tumor; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000235:genetics; D004268:DNA-Binding Proteins / Q000378:metabolism; D053595:Embryonic Stem Cells / Q000378:metabolism; D006801:Humans; D009474:Neurons / Q000166:cytology; D009687:Nuclear Proteins / Q000378:metabolism; D011401:Promoter Regions, Genetic; D014157:Transcription Factors / Q000737:chemistry* / Q000378:metabolism*; D000072160:Tumor Protein p73; D025521:Tumor Suppressor Proteins / Q000737:chemistry* / Q000378:metabolism*; D016335:Zinc Fingers; D050880:p300-CBP Transcription Factors / Q000378:metabolism*; D000099224:p300-CBP-Associated Factor
D018797:Cell Cycle Proteins; D050759:Cyclin-Dependent Kinase Inhibitor p21; D004268:DNA-Binding Proteins; D009687:Nuclear Proteins; D014157:Transcription Factors; D000072160:Tumor Protein p73; D025521:Tumor Suppressor Proteins; D050880:p300-CBP Transcription Factors; D000099224:p300-CBP-Associated Factor; C106464:PLAGL1 protein, human; C000606460:TP73 protein, human