| Structural highlights
Disease
SRCAP_HUMAN Floating-Harbor syndrome. The disease is caused by mutations affecting the gene represented in this entry.
Function
SRCAP_HUMAN Catalytic component of the SRCAP complex which mediates the ATP-dependent exchange of histone H2AZ/H2B dimers for nucleosomal H2A/H2B, leading to transcriptional regulation of selected genes by chromatin remodeling. Acts as a coactivator for CREB-mediated transcription, steroid receptor-mediated transcription, and Notch-mediated transcription.[1] [2] [3] [4] [5] [6]
Publication Abstract from PubMed
The conserved yeast SWR1 and human SRCAP chromatin remodeling complexes catalyze exchange of nucleosomal histone H2A for H2A.Z, but the underlying mechanism has remained obscure. Here, we show that histone exchange by SRCAP requires the transient activator CFDP1 and resolve nine cryo-electron microscopy structures of the SRCAP-CFDP1 holoenzyme that define the stepwise exchange mechanism. CFDP1 recognizes the conformation of the fully engaged SRCAP-nucleosome complex through interactions with multiple subunits-including direct contact with the ATPase domain-and induces conformational transitions that drive extensive DNA unwrapping, eviction of the H2A-H2B dimer, and insertion of the H2A.Z-H2B dimer, all without necessarily requiring hydrolysis of bound ATP. Collectively, these findings provide unprecedented insight into the mechanism of activator- and nucleotide-driven histone exchange from nucleosomal H2A to H2A.Z.
Structural mechanism of histone H2A.Z exchange by human SRCAP-CFDP1 holoenzyme.,Park G, Wu C, Louder RK Sci Adv. 2026 Jul 31;12(31):eaei7728. doi: 10.1126/sciadv.aei7728. Epub 2026 Jul , 31. PMID:42536744[7]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Johnston H, Kneer J, Chackalaparampil I, Yaciuk P, Chrivia J. Identification of a novel SNF2/SWI2 protein family member, SRCAP, which interacts with CREB-binding protein. J Biol Chem. 1999 Jun 4;274(23):16370-6. doi: 10.1074/jbc.274.23.16370. PMID:10347196 doi:https://dx.doi.org/10.1074/jbc.274.23.16370
- ↑ Monroy MA, Ruhl DD, Xu X, Granner DK, Yaciuk P, Chrivia JC. Regulation of cAMP-responsive element-binding protein-mediated transcription by the SNF2/SWI-related protein, SRCAP. J Biol Chem. 2001 Nov 2;276(44):40721-6. Epub 2001 Aug 24. PMID:11522779 doi:https://dx.doi.org/10.1074/jbc.M103615200
- ↑ Monroy MA, Schott NM, Cox L, Chen JD, Ruh M, Chrivia JC. SNF2-related CBP activator protein (SRCAP) functions as a coactivator of steroid receptor-mediated transcription through synergistic interactions with CARM-1 and GRIP-1. Mol Endocrinol. 2003 Dec;17(12):2519-28. Epub 2003 Sep 18. PMID:14500758 doi:https://dx.doi.org/10.1210/me.2003-0208
- ↑ Eissenberg JC, Wong M, Chrivia JC. Human SRCAP and Drosophila melanogaster DOM are homologs that function in the notch signaling pathway. Mol Cell Biol. 2005 Aug;25(15):6559-69. doi: 10.1128/MCB.25.15.6559-6569.2005. PMID:16024792 doi:https://dx.doi.org/10.1128/MCB.25.15.6559-6569.2005
- ↑ Ruhl DD, Jin J, Cai Y, Swanson S, Florens L, Washburn MP, Conaway RC, Conaway JW, Chrivia JC. Purification of a human SRCAP complex that remodels chromatin by incorporating the histone variant H2A.Z into nucleosomes. Biochemistry. 2006 May 2;45(17):5671-7. PMID:16634648 doi:https://dx.doi.org/10.1021/bi060043d
- ↑ Wong MM, Cox LK, Chrivia JC. The chromatin remodeling protein, SRCAP, is critical for deposition of the histone variant H2A.Z at promoters. J Biol Chem. 2007 Sep 7;282(36):26132-9. Epub 2007 Jul 8. PMID:17617668 doi:https://dx.doi.org/M703418200
- ↑ Park G, Wu C, Louder RK. Structural mechanism of histone H2A.Z exchange by human SRCAP-CFDP1 holoenzyme. Science advances. 2026 Jul 31. doi: 10.1126/sciadv.aei7728. PMID: 42536744.
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