PT  - JOURNAL ARTICLE
AU  - Sonia Zicari
AU  - Kalamo Farley
AU  - Lin Sun
AU  - Liam Spurr
AU  - Andrea Dragon
AU  - Michael Bukrinsky
AU  - Gary Simon
AU  - Ashok Chauhan
AU  - Mudit Tyagi
TI  - CBF-1 promotes the establishment and maintenance of HIV latency by recruiting Polycomb repressive complexes, PRC1 and PRC2, at HIV LTR
AID  - 10.1101/174607
DP  - 2017 Jan 01
TA  - bioRxiv
PG  - 174607
4099  - http://biorxiv.org/content/early/2017/08/10/174607.short
4100  - http://biorxiv.org/content/early/2017/08/10/174607.full
AB  - The C-promoter binding factor-1 (CBF-1) is a potent and specific inhibitor of the HIV-1 LTR promoter. Here we demonstrate that the knockdown of endogenous CBF-1 in latently infected primary CD4+ T cells, using specific small hairpin RNAs (shRNA), resulted in the reactivation of latent HIV proviruses. Chromatin immunoprecipitation (ChIP) assays using latently infected primary T cells and Jurkat T-cell lines demonstrated that CBF-1 induces the establishment and maintenance of HIV latency by recruiting Polycomb Group (PcG/PRC) corepressor complexes or Polycomb repressive complexes 1 and 2 (PRC1 and PRC2). Knockdown of CBF-1 resulted in the dissociation of PRCs corepressor complexes enhancing the recruitment of RNA polymerase II (RNAP II) at HIV LTR. Knockdown of certain components of PRC1 and PRC2 also led to the reactivation of latent proviruses. Similarly, treatment of latently infected primary CD4+ T cells with the EZH2 inhibitor, 3-deazaneplanocin A (DZNep), led to their reactivation.