AIDS, 2014, 01, 1719─1728

Genome-wide analysis of histone modifications in latently HIV-1 infected T cells

Jihwan Park, C Lim, S Ham, S Kim,B Choi, T Roh

Abstract

Objectives
The tranional silencing of human immunodeficiency virus type 1 (HIV-1) provirus in latently infected cells is a major hurdle on the pathway to HIV-1 elimination. The epigenetic mechanisms established by histone modifications may affect the tranional silencing of HIV-1 and viral latency. A systematic epigenome profiling could be applicable to develop new epigenetic diagnostic markers for detecting HIV-1 latency. Design: The HIV-1 latency cell lines (NCHA1, NCHA2, and ACH2) were compared to CD4þ T cell line (A3.01).
Methods
The histone modification profiles obtained from chromatin immunoprecipiation followed by sequencing (ChIP-Seq) for histone H3K4me3 and H3K9ac were systematically examined and differential gene expression patterns along with levels of histone modifications were used for network analysis.
Results
The HIV-1 latency gave rise to down-regulation of histone H3K4me3 and H3K9ac levels in 387 and 493 regions and up-regulation in 451 and 962 sites, respectively. By network analysis, 5 gene clusters were associated with down-regulated histone modifications and 6 gene clusters came up with up-regulated histone modifications. Integration of gene expression with epigenetic information revealed that the cell cycle regulatory genes such as CDKN1A (p21) and cyclin D2 (CCND2) identified by differentially modified histones might be an important role in maintaining the HIV-1 latency.
Conclusions
The tranional regulation by epigenetic memory should play a key role in the evolution and maintenance of HIV-1 latency accompanied by modulation of signaling molecules in the host cells.

• ISBN or ISSN: 0269-9370

• 본 연구는 질병관리본부 연구개발과제(과제번호 2010-N51001-00) 연구비를 지원받아 수행되었습니다.
• This research was supported by a fund(code 2010-N51001-00) by Research of Korea Centers for Disease Control and Prevention.