title: Involvement of histone methyltransferase GLP in HIV-1 latency through catalysis of H3K9 dimethylation.
abstract: Understanding the mechanism of HIV-1 latency is crucial to eradication of the viral reservoir in HIV-1-infected individuals. However, the role of histone methyltransferase (HMT) G9a-like protein (GLP) in HIV-1 latency is still unclear. In the present work, we established four clonal cell lines containing HIV-1 vector. We found that the integration sites of most clonal cell lines favored active gene regions. However, we also observed hypomethylation of CpG of HIV 5'LTR in all four clonal cell lines. Additionally, 5'-deoxy-5'-methylthioadenosine (MTA), a broad-spectrum histone methyltransferase inhibitor, was used to examine the role of histone methylation in HIV-1 latency. MTA was found to decrease the level of H3K9 dimethylation, causing reactivation of latent HIV-1 in C11 cells. GLP knockdown by small interfering RNA clearly induced HIV-1 LTR expression. Results suggest that GLP may play a significant role in the maintenance of HIV-1 latency by catalyzing dimethylation of H3K9.
authors.affiliation: State key Laboratory of Genetic Engineering, Institute of Genetics, School of Life Sciences, Fudan University, Shanghai 200433, China.
authors.forename: Donglin
authors.initials: D
authors.lastname: Ding
authors.forename: Xiying
authors.initials: X
authors.lastname: Qu
authors.forename: Lin
authors.initials: L
authors.lastname: Li
authors.forename: Xin
authors.initials: X
authors.lastname: Zhou
authors.forename: Sijie
authors.initials: S
authors.lastname: Liu
authors.forename: Shiguan
authors.initials: S
authors.lastname: Lin
authors.forename: Pengfei
authors.initials: P
authors.lastname: Wang
authors.forename: Shaohui
authors.initials: S
authors.lastname: Liu
authors.forename: Chuijin
authors.initials: C
authors.lastname: Kong
authors.forename: Xiaohui
authors.initials: X
authors.lastname: Wang
authors.forename: Lin
authors.initials: L
authors.lastname: Liu
authors.forename: Huanzhang
authors.initials: H
authors.lastname: Zhu
mesh_terms: D002460:Cell Line; D055785:Gene Knockdown Techniques; D015497:HIV-1 / Q000472:pathogenicity* / Q000502:physiology; D006649:Histocompatibility Antigens / Q000235:genetics / Q000378:metabolism*; D011495:Histone-Lysine N-Methyltransferase / Q000235:genetics / Q000378:metabolism*; D006657:Histones / Q000378:metabolism*; D006801:Humans; D008745:Methylation; D014775:Virus Activation; D017735:Virus Latency
chemical_list: D006649:Histocompatibility Antigens; D006657:Histones; C445405:EHMT2 protein, human; D011495:Histone-Lysine N-Methyltransferase