Puri P L, Sartorelli V, Yang X J, Hamamori Y, Ogryzko V V, Howard B H, Kedes L, Wang J Y, Graessmann A, Nakatani Y, Levrero M
Laboratory of Gene Expression, Fondazione Andrea Cesalpino, Istituto I Clinica Medica, Policlinico Umberto I, University of Rome, La Sapienza, Italy.
Mol Cell. 1997 Dec;1(1):35-45. doi: 10.1016/s1097-2765(00)80005-2.
PCAF is a histone acetyltransferase that associates with p300/CBP and competes with E1A for access to them. While exogenous expression of PCAF potentiates both MyoD-directed transcription and myogenic differentiation, PCAF inactivation by anti-PCAF antibody microinjection prevents differentiation. MyoD interacts directly with both p300/CBP and PCAF, forming a multimeric protein complex on the promoter elements. Viral transforming factors that interfere with muscle differentiation disrupt this complex without affecting the MyoD-DNA interaction, indicating functional significance of the complex formation. Exogenous expression of PCAF or p300 promotes p21 expression and terminal cell-cycle arrest. Both of these activities are dependent on the histone acetyltransferase activity of PCAF, but not on that of p300. These results indicate that recruitment of histone acetyltransferase activity of PCAF by MyoD, through p300/CBP, is crucial for activation of the myogenic program.
PCAF是一种组蛋白乙酰转移酶，它与p300/CBP结合，并与E1A竞争接近它们的机会。虽然PCAF的外源性表达增强了MyoD指导的转录和成肌分化，但通过抗PCAF抗体显微注射使PCAF失活会阻止分化。MyoD直接与p300/CBP和PCAF相互作用，在启动子元件上形成多聚体蛋白复合物。干扰肌肉分化的病毒转化因子会破坏这种复合物，而不影响MyoD与DNA的相互作用，这表明复合物形成具有功能意义。PCAF或p300的外源性表达促进p21表达和终末细胞周期停滞。这两种活性都依赖于PCAF的组蛋白乙酰转移酶活性，而不依赖于p300的活性。这些结果表明，MyoD通过p300/CBP募集PCAF的组蛋白乙酰转移酶活性对于激活成肌程序至关重要。
