Bimodal high-affinity association of Brd4 with murine leukemia virus integrase and mononucleosomes.

ABSTRACT: The importance of understanding the molecular mechanisms of murine leukemia virus (MLV) integration into host chromatin is highlighted by the development of MLV-based vectors for human gene-therapy. We have recently identified BET proteins (Brd2, 3 and 4) as the main cellular binding partners of MLV integrase (IN) and demonstrated their significance for effective MLV integration at transcription start sites. Here we show that recombinant Brd4, a representative of the three BET proteins, establishes complementary high-affinity interactions with MLV IN and mononucleosomes (MNs). Brd4(1-720) but not its N- or C-terminal fragments effectively stimulate MLV IN strand transfer activities in vitro. Mass spectrometry- and NMR-based approaches have enabled us to map key interacting interfaces betwe

SUBMITTER: Larue RC 

PROVIDER: S-EPMC4005663 | biostudies-literature | 2014 Apr

REPOSITORIES: biostudies-literature