%0 Journal Article
%T Spt6 levels are modulated by PAAF1 and proteasome to regulate the HIV-1 LTR
%A Mirai Nakamura
%A Poornima Basavarajaiah
%A Emilie Rousset
%A Cyprien Beraud
%A Daniel Latreille
%A Im¨¨ne-Sarah Henaoui
%A Irina Lassot
%A Bernard Mari
%A Rosemary Kiernan
%J Retrovirology
%D 2012
%I BioMed Central
%R 10.1186/1742-4690-9-13
%X Here, we show that Spt6 is targeted by proteasome in the absence of PAAF1. PAAF1 interacts with the N-terminus of Spt6, suggesting that PAAF1 protects Spt6 from proteolysis. Depletion of either PAAF1 or Spt6 reduced histone occupancy at the HIV-1 promoter, and induced the synthesis of aberrant transcripts. Ectopic Spt6 expression or treatment with proteasome inhibitor partially rescued the transcription defect associated with loss of PAAF1. Transcriptional profiling followed by ChIP identified a subset of cellular genes that are regulated in a similar fashion to HIV-1 by Spt6 and/or PAAF1, including many that are involved in cancer, such as BRCA1 and BARD1.These results show that intracellular levels of Spt6 are fine-tuned by PAAF1 and proteasome, which is required for HIV-1 transcription and extends to cellular genes implicated in cancer.Spt6 is a highly conserved transcription factor that plays a number of distinct roles during transcription. It interacts directly with histones, particularly H3, and possesses nucleosome assembly activity in vitro [1]. Together with FACT, a H2A/H2B chaperone, Spt6 restores chromatin structure in the wake of elongating RNAPII [2,3]. Loss of Spt6 disrupts normal chromatin structure and leads to the initiation of cryptic transcripts from within the coding region [3]. At inducible genes, Spt6 is required to restore transcriptional repression by promoting nucleosome reassembly over the promoter region [4,5]. Spt6 is a transcription elongation factor that is associated with the body of genes during transcription [6,7] and enhances the elongation rate of RNAPII, even on naked DNA [8,9]. It contains tandem SH2 domains that interact with phosphorylated Ser2 and Ser5 of the carboxy-terminal domain (CTD) of RNAPII [10,11]. Spt6 is also implicated in mRNA processing through interactions with the nuclear exosome subunit, Rrp6, and Iws1 that recruits RNA processing/export factors Ref1/Aly [11,12], and prevents premature 3' processing at cryptic,
%K LTR
%K transcription
%K Tat
%K Spt6
%K PAAF1
%K proteasome
%U http://www.retrovirology.com/content/9/1/13