EP400 subfamily

E1A binding Protein p400, which appears to have a role in regulation of E1A-activated genes 1, 2, 3. EP400 has been shown to interact strongly with ruvB-like helicases TAP54α/β in the TRRAP/TIP60 histone acetyl transferase complex 1.

The relationship between the EP400 and Swr1 subfamilies is complex. The subfamily HMM profiles clearly distinguish EP400 from Swr1 members, and show that EP400 members are restricted to vertebrates whereas Swr1 subfamily members are found in almost all eukaryotes.

Although most vertebrate genomes contain a gene each for an Swr1 and EP400 member, zebrafish, mouse, rat and chicken appear to have either one or the other. The subfamilies nevertheless share a number of close similarities in primary sequence. Firstly, the consensus for the common helicase-like regions share some 50% identity. Secondly, the animal members of both subfamilies contain large insertions rich in proline and serine/threonine at the major insertion site. Thirdly, although these insertions are of reduced complexity, there appear to be blocks of homology between human EP400 and SRCAP within the region.

Members of the two families also containing overlapping combinations of accessory domains outside the helicase-like region. D melanogaster Swr1 subfamily member DominoA and human EP400 both contain SANT domains, whereas human Swr1 subfamily member SRCAP instead contains an AT hook 4.

Based on the accessory domain combination, EP400 is sometimes referred to as hDomino although D melanogaster Domino has higher homology with human SRCAP than EP400 1 and SRCAP can complement Domino mutants 4. There have also been suggestions that D melanogaster alternative splice isoforms DominoA and DominoB are functional homologues of EP400 and SRCAP 4, although both isoforms contain the same helicase-like and proline/serine/threonine-rich major insertion region.

Similarly, it has been suggested that S cerevisiae Eaf1p is a homologue of human EP400, although Eaf1p lacks both Snf2-related helicase-like and extended proline-rich regions 5. In addition to the complexity in primary sequence relationships, complexes of potentially overlapping composition exist involving human EP400 and SRCAP including the NCoR-1 histone deacetylase 6, TRRAP/TIP60 histone acetylase 1, 7, 8 and DMAP1 complex 9.

Despite the existence of a clear distinction between helicase-like regions for the EP400 and Swr1 subfamilies, their relatively recent divergence, extensive overlap of interaction partners, and the complexity of the chromatin processes in which they are involved suggests that these two families maintain a close functional relationship.

names associated with subfamily members
E1A binding proten p400, TNRC12, hDomino
1: Fuchs, M., J. Gerber, et al. (2001). The p400 complex is an essential E1A transformation target. Cell 106(3): 297-307. PubMed
2: Chan, H. M., M. Narita, et al. (2005). The p400 E1A-associated protein is a novel component of the p53 --> p21 senescence pathway. Genes Dev 19(2): 196-201. PubMed
3: Samuelson, A. V., M. Narita, et al. (2005). p400 is required for E1A to promote apoptosis. J Biol Chem 280(23): 21915-23. PubMed
4: Eissenberg, J. C., M. Wong, et al. (2005). Human SRCAP and Drosophila melanogaster DOM are homologs that function in the notch signaling pathway. Mol Cell Biol 25(15): 6559-69. PubMed
5: Doyon, Y. and J. Cote (2004). The highly conserved and multifunctional NuA4 HAT complex. Curr Opin Genet Dev 14(2): 147-54. PubMed
6: Underhill, C., M. S. Qutob, et al. (2000). A novel nuclear receptor corepressor complex, N-CoR, contains components of the mammalian SWI/SNF complex and the corepressor KAP-1. J Biol Chem 275(51): 40463-70. PubMed
7: Cai, Y., J. Jin, et al. (2003). Identification of new subunits of the multiprotein mammalian TRRAP/TIP60-containing histone acetyltransferase complex. J Biol Chem 278(44): 42733-6. PubMed
8: Cai, Y., J. Jin, et al. (2005). The mammalian YL1 protein is a shared subunit of the TRRAP/TIP60 histone acetyltransferase and SRCAP complexes. J Biol Chem 280(14): 13665-70. PubMed
9: Doyon, Y., W. Selleck, et al. (2004). Structural and functional conservation of the NuA4 histone acetyltransferase complex from yeast to humans. Mol Cell Biol 24(5): 1884-96. PubMed