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Application of MassSQUIRM for Quantitative Measurements of Lysine Demethylase Activity
Published on: March 11, 2012
Lysine-specific demethylase 1 cooperates with BRAF-histone deacetylase complex 80 to enhance HIV-1 Tat-mediated
1Laboratory of Medical Molecular Virology, School of Medicine, Nankai University, 94 Weijin Road, Nankai District, Tianjin, 300071, China.
Abstract:
Despite the notable success of combination antiretroviral therapy, how to eradicate latent HIV-1 from reservoirs poses a challenge. The Tat protein plays an indispensable role in HIV reactivation and histone demethylase LSD1 promotes Tat-mediated long terminal repeats (LTR) activation. However, the role of LSD1 in remodeling chromatin and the role of its component BHC80 in activation of latent HIV-1 in T cells are unknown. Our findings indicate that LSD1 could decrease the level of histone H3 lysine 4 trimethylation (H3K4me3) at the HIV-1 promoter by recruiting histone lysine demethylase 5A (KDM5A) and preventing histone methyltransferase Set1A and WD-40 repeat protein 5 (WDR5) from binding to LTR. Moreover, BHC80 is necessary for LSD1-triggered LTR activation and assists LSD1 in activating LTR by binding to nucleotides 305-631 of LTR. In activated J-Lat-A2 cells, BHC80 expression was elevated and its isoform BHC80-6 promoted the association of BHC80 with LSD1. These results suggest that the LSD1-BHC80 complex enhances HIV-1 transcription by a decrease of H3K4me3 level at the viral promoter. Therefore, it might be used as a new drug target to reactivate latent HIV-1.
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