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


METHODS
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.


CONCLUSIONS
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.
Jihwan
J
Park
Chae Hyun
CH
Lim
Seokjin
S
Ham
Sung Soon
SS
Kim
Byeong-Sun
BS
Choi
Tae-Young
TY
Roh
D047369:Chromatin Immunoprecipitation; D044127:Epigenesis, Genetic; D020869:Gene Expression Profiling; D053263:Gene Regulatory Networks; D015658:HIV Infections / Q000821:virology; D015497:HIV-1 / Q000502:physiology*; D006657:Histones / Q000378:metabolism*; D006801:Humans; D011499:Protein Processing, Post-Translational; D017422:Sequence Analysis, DNA; D013601:T-Lymphocytes / Q000821:virology*; D017735:Virus Latency
D006657:Histones