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

Park, Jihwana; Lim, Chae Hyunb; Ham, Seokjina; Kim, Sung Soonc; Choi, Byeong-Sunc; Roh, Tae-Younga,b

doi: 10.1097/QAD.0000000000000309
Basic Science

Objectives: The transcriptional silencing of HIV 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 transcriptional 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 with CD4+ 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 downregulation of histone H3K4me3 and H3K9ac levels in 387 and 493 regions and upregulation in 451 and 962 sites, respectively. By network analysis, five gene clusters were associated with downregulated histone modifications and six gene clusters came up with upregulated 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 play an important role in maintaining the HIV-1 latency.

Conclusion: The transcriptional regulation by epigenetic memory should play a key role in the evolution and maintenance of HIV-1 latency accompanied by modulation of signalling molecules in the host cells.

aDepartment of Life Sciences

bDivision of Integrative Biosciences and Biotechnology, Pohang University of Science and Technology (POSTECH), Pohang

cDivision of AIDS, Center for Immunology and Pathology, Korea National Institutes of Health, Cheongwon, Republic of Korea.

Correspondence to Tae-Young Roh, PhD, Pohang University of Science and Technology (POSTECH), Pohang 790784, Republic of Korea and Byeong-Sun Choi, PhD, Korea National Institutes of Health, Cheongwon, Republic of Korea. Tel: +82 54 279 2350; fax: +82 54 279 8179; e-mail: tyroh@postech.edu,byeongsun@korea.kr

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Received December 13, 2013

Accepted April 14, 2014

© 2014 Lippincott Williams & Wilkins, Inc.