Bowman Tamara A, Wong Madeline M, Cox Linda K, Baldassare Joseph J, Chrivia John C
Department of Pharmacological and Physiological Science, Saint Louis University School of Medicine, 1402 South Grand Boulevard, Saint Louis, MO 63104, USA.
Int J Cell Biol. 2011;2011:715642. doi: 10.1155/2011/715642. Epub 2011 May 29.
The p400 and SRCAP (Snf2-related CBP activator protein) complexes remodel chromatin by catalyzing deposition of histone H2A.Z into nucleosomes. This remodeling activity has been proposed as a basis for regulation of transcription by these complexes. Transcript levels of p21 or Sp1 mRNAs after knockdown of p400 or SRCAP reveals that each regulates transcription of these promoters differently. In this study, we asked whether deposition of H2A.Z within specific nucleosomes by p400 or SRCAP dictates transcriptional activity. Our data indicates that nucleosome density at specific p21 or Sp1 promoter positions is not altered by the loss of either remodeling complex. However, knockdown of SRCAP or p400 reduces deposition of H2A.Z∼50% into all p21 and Sp1 promoter nucleosomes. Thus, H2A.Z deposition is not targeted to specific nucleosomes. These results indicate that the deposition of H2A.Z by the p400 or SRCAP complexes is not sufficient to determine how each regulates transcription. This conclusion is further supported by studies that demonstrate a SRCAP(ΔATP ) mutant unable to deposit H2A.Z has similar transcriptional activity as wild-type SRCAP.
p400和SRCAP（与Snf2相关的CBP激活蛋白）复合物通过催化组蛋白H2A.Z沉积到核小体中对染色质进行重塑。这种重塑活性被认为是这些复合物调控转录的基础。敲低p400或SRCAP后p21或Sp1 mRNA的转录水平表明，它们对这些启动子转录的调控方式各不相同。在本研究中，我们探究了p400或SRCAP在特定核小体内沉积H2A.Z是否决定转录活性。我们的数据表明，缺失任何一种重塑复合物都不会改变特定p21或Sp1启动子位置的核小体密度。然而，敲低SRCAP或p400会使所有p21和Sp1启动子核小体中H2A.Z的沉积减少约50%。因此，H2A.Z的沉积并非靶向特定核小体。这些结果表明，p400或SRCAP复合物介导的H2A.Z沉积不足以决定它们各自对转录的调控方式。一项研究进一步支持了这一结论，该研究表明，无法沉积H2A.Z的SRCAP(ΔATP)突变体具有与野生型SRCAP相似的转录活性。
