Identification of a Novel SNF2/SWI2 Protein Family Member, SRCAP, Which Interacts with CREB-binding Protein

Abstract

The ability of cAMP response-element binding protein (CREB)-binding protein (CBP) to function as a co-activator for a number of transcription factors appears to be mediated by its ability to act as a histone acetyltransferase and through its interaction with a number of other proteins (general transcription factors, histone acetyltransferases, and other co-activators). Here we report that CBP also interacts with a novel ATPase termed Snf2-Related CBP Activator Protein (SRCAP). Consistent with this activity, SRCAP contains the conserved ATPase domain found within members of the Snf2 family. Transfection experiments demonstrate that SRCAP is able to activate transcription when expressed as a Gal-SRCAP chimera and that SRCAP also enhances the ability of CBP to activate transcription. The adenoviral protein E1A was found to disrupt interaction between SRCAP and CBP possibly representing a mechanism for E1A-mediated transcriptional repression. CREB 1 -binding protein (CBP) has been found to function as a co-activator for a growing number of sequence specific transcription factors including CREB, the STATs, and the nuclear receptors (1-5). Binding studies have identified several regions of CBP that interact with general transcription factors such as TBP, TFIIB, and RNAP II (2, 6 -8), suggesting it functions as a co-activator in part by recruiting these proteins to the promoter. CBP has also been shown to have intrinsic histone acetyltransferase (HAT) activity and to bind to several proteins with HAT activity (P/CAF, ACTR, NCoA-1). This suggests that CBP alone, or acting in conjunction with these proteins, functions as a co-activator by stimulating remodeling of chromatin (9 -12). This is supported by the work of Korus et al. (13) who demonstrate that several transcription factors have a specific requirement for the HAT activity of NCoAs, P/CAF, and CBP for activation of transcription. The adenoviral protein E1A also binds CBP but represses the ability of CBP to function as a co-activator for CREB as well as a number of other transcription factors (4,5,14,15). This appears to be due in part to the ability of E1A to prevent binding of P/CAF and P/CIP to the C-terminal end of CBP. E1A also binds to the N-terminal end of CBP and suppresses the ability of a Gal-CBP-(1-450) chimera to activate transcription. Although P/CAF also binds to this same region, competition between P/CAF and E1A binding has not been demonstrated (5).Deletion of amino acids 1-460 abolishes the ability of CBP to serve as a co-activator for CREB and STAT-1 but not for other transcription factors such as the retinoic acid receptor (5, 6). In "squelching-type" assays, overexpression of CBP amino acids 1-460 has also been found to block the ability of full-length CBP to activate CREB-mediated transcription (5). Studies from several laboratories indicate that this region of CBP contacts proteins, including TBP and P/CAF, which may be involved in the activation of transcription (5, 6). Microinjection studies support such a role for P/CAF by demonstrating ...

The Chromatin Remodeling Protein, SRCAP, Is Critical for Deposition of the Histone Variant H2A.Z at Promoters

“…In summary, previous to this work it was known that in transient transfection assays SRCAP functions to activate transcription (17,18), and in vitro studies in our laboratory indicated that it catalyzes incorporation of H2A.Z into nucleosomes (16). The current work completes the picture as to how SRCAP may regulate transcription.…”

“…It is not clear, however, whether the decreased transcription observed results solely from the loss of H2A.Z incorporation or whether the loss of other SRCAP activities is a contributor. This latter possibility is suggested by our studies indicating that SRCAP contains several additional domains capable of activating transcription independent of the histone exchange reaction (17,18).…”

“…SRCAP recruitment might occur through interaction with coactivators such as the histone acetyltransferase CBP (17,18), the p160 coactivator (GRIP1), and the methyltransferase CARM-1 (17). Alternatively, SRCAP may be recruited to nucleosomes containing specific histone modifications.…”

A Novel Nuclear Receptor Corepressor Complex, N-CoR, Contains Components of the Mammalian SWI/SNF Complex and the Corepressor KAP-1

“…Four of the proteins identified by mass spectrometry belong to the SWI/SNF family of proteins and include the BRG1-associated factor (BAF) 170, BAF 155, BAF 47/INI1, and the SWI/SNF-related CBP activator protein (SRCAP) (40). BAF 170 and BAF 155 are highly similar homolog of the yeast SWI3 protein, whereas BAF 47/INI1 represents the mammalian homolog of the yeast SNF5 protein.…”

Reconciling the positive and negative roles of histone H2A.Z in gene transcription

“…29 We have also shown that p400 is able to directly interact with the ERα, which could be responsible for the recruitment of the complex to ERα target genes, and subsequent H2A.Z incorporation. 30 Furthermore, a similar scenario could be possible for SRCAPmediated incorporation of H2A.Z since it interacts with the CREB-binding protein (CBP) co-activator, 48 which in turn interacts with several transcriptional activators. 49,50 Additionally, another study has shown a strong correlation between the presence of Myc and that of H2A.Z to promoter regions.…”