Regulation of the homeodomain CCAAT displacement/cut protein function by histone acetyltransferases p300/CREB-binding protein (CBP)-associated factor and CBP.
The CCAAT displacement protein/cut homologue (CDP/cut) is a divergent homeodomain protein that is highly conserved through evolution and has properties of a potent transcriptional repressor. CDP/cut contains three conserved cut-repeat domains and a conserved homeobox, each involved in directing binding specificity to unique nucleotide sequence elements. Furthermore, CDP/cut may play a role as a structural component of chromatin through its direct interaction with nucleosomal DNA and association with nuclear matrix attachment regions. CDP/cut is cell-cycle regulated through interactions with Rb, p107, specific kinases and phosphatases directing the transcriptional activity of CDP/cut on such genes encoding p21(WAF1,CIP1), c-myc, thymidine kinase, and histones. Our previous studies indicate that CDP/cut is associated with histone deacetylase activity and is associated with a corepressor complex through interactions with histone deacetylases. Here, we report the interaction of CDP/cut with CBP and p300/CREB-binding protein-associated factor (PCAF) along with the modification of CDP/cut by the histone acetyltransferase PCAF. Acetylation of CDP/cut by PCAF is directed at conserved lysine residues near the homeodomain region and regulates CDP/cut function. These observations are consistent with the ability of CDP/cut to regulate genes as a transcriptional repressor, suggesting acetylation as a mechanism that regulates CDP/cut function.
Li
S
S
Department of Pediatrics, Mount Sinai School of Medicine of New York University, New York, NY 10029, USA.
Aufiero
B
B
Schiltz
R L
RL
Walsh
M J
MJ
D000123:Acetyltransferases / Q000378:metabolism*; D000595:Amino Acid Sequence; D000818:Animals; D050882:CREB-Binding Protein; D018797:Cell Cycle Proteins / Q000378:metabolism*; D006367:HeLa Cells; D051548:Histone Acetyltransferases; D018398:Homeodomain Proteins / Q000378:metabolism; D006801:Humans; D051379:Mice; D008969:Molecular Sequence Data; D009687:Nuclear Proteins / Q000378:metabolism*; D012097:Repressor Proteins / Q000378:metabolism*; D015398:Signal Transduction; D015534:Trans-Activators / Q000378:metabolism*; D014157:Transcription Factors; D050880:p300-CBP Transcription Factors; D000099224:p300-CBP-Associated Factor
D000123:Acetyltransferases; D050882:CREB-Binding Protein; D018797:Cell Cycle Proteins; D051548:Histone Acetyltransferases; D018398:Homeodomain Proteins; D009687:Nuclear Proteins; D012097:Repressor Proteins; D015534:Trans-Activators; D014157:Transcription Factors; D050880:p300-CBP Transcription Factors; D000099224:p300-CBP-Associated Factor; C080632:CUX1 protein, human; C000624101:Cux1 protein, mouse; C494363:CREBBP protein, human; C494364:Crebbp protein, mouse