University of Strasbourg, EA4438, Institute of parasitology, Strasbourg, France.
Nucleic Acids Res. 2012 Mar;40(5):1904-15. doi: 10.1093/nar/gkr857. Epub 2011 Nov 8.
Microglial cells are the main HIV-1 targets in the central nervous system (CNS) and constitute an important reservoir of latently infected cells. Establishment and persistence of these reservoirs rely on the chromatin structure of the integrated proviruses. We have previously demonstrated that the cellular cofactor CTIP2 forces heterochromatin formation and HIV-1 gene silencing by recruiting HDAC and HMT activities at the integrated viral promoter. In the present work, we report that the histone demethylase LSD1 represses HIV-1 transcription and viral expression in a synergistic manner with CTIP2. We show that recruitment of LSD1 at the HIV-1 proximal promoter is associated with both H3K4me3 and H3K9me3 epigenetic marks. Finally, our data suggest that LSD1-induced H3K4 trimethylation is linked to hSET1 recruitment at the integrated provirus.
小胶质细胞是中枢神经系统（CNS）中 HIV-1 的主要靶细胞，构成潜伏感染细胞的重要储存库。这些储存库的建立和维持依赖于整合前病毒的染色质结构。我们之前已经证明，细胞共因子 CTIP2 通过在整合的病毒启动子处募集 HDAC 和 HMT 活性，迫使异染色质形成和 HIV-1 基因沉默。在本工作中，我们报告组蛋白去甲基酶 LSD1 与 CTIP2 协同抑制 HIV-1 的转录和病毒表达。我们表明，LSD1 在 HIV-1 近端启动子上的募集与 H3K4me3 和 H3K9me3 表观遗传标记都有关。最后，我们的数据表明，LSD1 诱导的 H3K4 三甲基化与整合前病毒中 hSET1 的募集有关。
