PMID- 7964636 OWN - NLM STAT- MEDLINE DCOM- 19941201 LR - 20131121 IS - 0022-1317 (Print) IS - 0022-1317 (Linking) VI - 75 ( Pt 11) DP - 1994 Nov TI - Inhibition of human T cell leukaemia virus type I long terminal repeat expression by DNA methylation: implications for latency. PG - 3255-9 AB - Human T cell leukaemia virus type I (HTLV-I) provirus DNA was found to be methylated in patients with adult T cell leukaemia. We have therefore examined the possibility that DNA methylation might contribute to HTLV-I latency. In vitro methylation of HTLV-I long terminal repeat (LTR)-chloramphenicol acetyltransferase or LTR-Luciferase constructs at eight HpaII sites, a subset of the eukaryotic methylation site CpG, resulted in a three- to fourfold inhibition of transcription in transfected cells. Inhibition of transcription by methylation of all CpG methylation sites using SssI methylase was much more pronounced (50- to 80-fold). As partial methylation of the LTR showed, methylation of the promoter region was responsible for most of the effect. Whereas cellular stimulation by a combination of phorbol 12-myristate 13-acetate and Tax was able to reverse the HpaII methylation effect, the inhibition by SssI methylation was not suppressible under these conditions. The results are in line with a possible function of DNA methylation in HTLV-I latency. FAU - Cassens, S AU - Cassens S AD - Abteilung Virologie, Robert Koch-Institut, Berlin, Germany. FAU - Ulrich, U AU - Ulrich U FAU - Beimling, P AU - Beimling P FAU - Simon, D AU - Simon D LA - eng PT - Journal Article PL - England TA - J Gen Virol JT - The Journal of general virology JID - 0077340 RN - 0 (DNA, Viral) RN - 0 (Gene Products, tax) RN - EC 1.13.12.- (Luciferases) RN - EC 2.1.1.- (DNA modification methylase HpaII) RN - EC 2.1.1.- (DNA-Cytosine Methylases) RN - EC 2.3.1.28 (Chloramphenicol O-Acetyltransferase) RN - NI40JAQ945 (Tetradecanoylphorbol Acetate) SB - IM MH - Adult MH - Base Sequence MH - Chloramphenicol O-Acetyltransferase/biosynthesis MH - DNA, Viral/chemistry/*metabolism MH - DNA-Cytosine Methylases/metabolism MH - Gene Products, tax/metabolism MH - Human T-lymphotropic virus 1/*genetics/isolation & purification/physiology MH - Humans MH - Leukemia, T-Cell/virology MH - Luciferases/biosynthesis MH - Methylation MH - *Repetitive Sequences, Nucleic Acid MH - Restriction Mapping MH - Tetradecanoylphorbol Acetate/pharmacology MH - *Transcription, Genetic EDAT- 1994/11/01 00:00 MHDA- 1994/11/01 00:01 CRDT- 1994/11/01 00:00 PHST- 1994/11/01 00:00 [pubmed] PHST- 1994/11/01 00:01 [medline] PHST- 1994/11/01 00:00 [entrez] AID - 10.1099/0022-1317-75-11-3255 [doi] PST - ppublish SO - J Gen Virol. 1994 Nov;75 ( Pt 11):3255-9. doi: 10.1099/0022-1317-75-11-3255.