Identification of New Subunits of the Multiprotein Mammalian TRRAP/TIP60-containing Histone Acetyltransferase Complex

Abstract

The mammalian ATM/PI 3-kinase-related TRRAP protein was previously found to be a component of a multiprotein histone acetyltransferase (HAT) complex containing the HAT TIP60. In this report, we identify a previously uncharacterized protein encoded by the FLJ10914 ORF, which we designate MRGBP, as a new component of the TRRAP/TIP60 HAT complex. In addition, through purification of MRGBP and its associated proteins from HeLa cell nuclear extracts, we identify the thyroid receptor coactivating protein (TRCp120), DMAP1, and the related MRG15 and MRGX proteins as MRGBP-associating proteins, and we present biochemical evidence that they are previously unrecognized components of the TRRAP/TIP60 HAT complex. Taken together, our findings shed new light on the structure and function of the mammalian TRRAP/TIP60 histone acetyltransferase complex.