LEDGF/p75 interacts with mRNA splicing factors and targets HIV-1 integration to highly spliced genes.

ABSTRACT: The host chromatin-binding factor LEDGF/p75 interacts with HIV-1 integrase and directs integration to active transcription units. To understand how LEDGF/p75 recognizes transcription units, we sequenced 1 million HIV-1 integration sites isolated from cultured HEK293T cells. Analysis of integration sites showed that cancer genes were preferentially targeted, raising concerns about using lentivirus vectors for gene therapy. Additional analysis led to the discovery that introns and alternative splicing contributed significantly to integration site selection. These correlations were independent of transcription levels, size of transcription units, and length of the introns. Multivariate analysis with five parameters previously found to predict integration sites showed that intron density is th

SUBMITTER: Singh PK 

PROVIDER: S-EPMC4647561 | biostudies-literature | 2015 Nov

REPOSITORIES: biostudies-literature