%0 Journal Article
%T Loss of H2A.Z Is Not Sufficient to Determine Transcriptional Activity of Snf2-Related CBP Activator Protein or p400 Complexes
%A Tamara A. Bowman
%A Madeline M. Wong
%A Linda K. Cox
%A Joseph J. Baldassare
%A John C. Chrivia
%J International Journal of Cell Biology
%D 2011
%I Hindawi Publishing Corporation
%R 10.1155/2011/715642
%X 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¦¤ATP mutant unable to deposit H2A.Z has similar transcriptional activity as wild-type SRCAP. 1. Introduction The histone variant H2A.Z has been shown to have multiple functions in mammalian cells. It is essential for embryonic development, proper segregation of chromosomes [1, 2], and a number of studies indicate it plays a role in both activation and repression of transcription [3¨C5]. Aberrant H2A.Z expression may also play a role in some human diseases, since it has been demonstrated to play a role in cardiac hypertrophy [6] and H2A.Z levels are elevated in breast cancer [7, 8]. Recent studies have examined the genomewide distribution of H2A.Z in human cells. These studies found that nucleosomes located in promoter regions are highly enriched in H2A.Z, indicating a positive correlation that exists between gene activity and H2A.Z deposition [9, 10]. The deposition of H2A.Z at these sites has been hypothesized to promote organization of nucleosomes at the promoter providing the optimal architecture for activation of transcription. How incorporation of H2A.Z into nucleosomes functions to increase promoter organization and contribute to regulation of transcription is not clear. Several studies indicate that nucleosomes comprised of recombinant H2A.Z or native chicken erythrocyte H2A.Z are more stable than H2A-containing nucleosomes [11, 12]. Other studies, however, have raised the possibility that in certain circumstances, when nucleosomes also contain the histone variant H3.3, H2A.Z decreases nucleosome
%U http://www.hindawi.com/journals/ijcb/2011/715642/