Abstract
HIV-1 methylation binding protein-1 (HMBP-1) (formerly called HMBP) is a protein found in human cell nuclei that binds with enhanced affinity to a fragment of the HIV-1 long terminal repeat sequence (LTR) containing three Sp1 sites when all three sites are methylated. HMBP-2 is another protein present in the nuclei of human T helper lymphocytes and HeLa cells that binds to the HIV-1 LTR. HMBP-2 binds preferentially to the same region of the HIV-1 LTR as does HMBP-1, but HMBP-2 binds best when only one of the three Sp1 sites is methylated. HMBP-2 can be separated from HMBP-1 chromatographically, and dimethyl sulfate (DMS) methylation interference analysis indicates that their binding sites are not identical. HMBP-2 represents a novel protein factor capable of binding to a partially methylated region of the HIV-1 LTR.
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References
Bednarik DP, Cook JA, Pitha PM. Inactivation of the HIV LTR by DNA CpG methylation: evidence for a role in latency. EMBO J 9:1157–1164;1990.
Bednarik DP, Duckett C, Kim SU, Perez VL, Griffis K, Guenthner PC, Folks TM. DNA CpG methylation inhibits binding of NF-κB protein to the HIV-1 long terminal repeat cognate DNA motifs. New Biol 3:969–976;1990.
Bednarik DP, Folks TM. The mechanism of HIV latency. AIDS 6:3–16;1992.
Ben-Hattar J, Beard P, Jiricny J. Cytosine methylation in CTF and Sp1 recognition sites of an HSV tk promoter: effects on transcription in vivo and on factor binding in vitro. Nucleic Acids Res 17:10179–10190;1989.
Berkhout B, Jeang K-T. Functional roles for the TATA promoter and enhancers in basal and Tat-induced expression of the human immunodeficiency virus type 1 long terminal repeat. J Virol 66:139–149;1992.
Boyes J, Bird A. Repression of genes by DNA methylation depends on CpG density and promoter strength: evidence for involvement of a methyl-CpG binding protein. EMBO J 11:327–333;1992.
Doerfler W. The significance of DNA methylation patterns: promoter inhibition by sequence-specific methylation is one functional consequence. Philos Trans R Soc Lond B Biol Sci 326:253–265;1990.
Gatignol A, Duarte M, Daviet L, Chang Y-N, Jeang K-T. Sequential steps in Tat transactivation of HIV-1 mediated through cellular DNA, RNA, and protein binding factors. Gene Expr 5:217–228;1996.
Gilmartin GM, Nevins JR. An ordered pathway of assembly of components required for polyadenylation site recognition and processing. Genes Dev 3:2180–2190;1989.
Jane SM, Gumucio DL, Ney PA, Cunningham JM, Nienhuis AW. Methylation-enhanced binding of Sp1 to the stage selector element of the human r-globin gene promoter may regulate developmental specificity of expression. Mol Cell Biol 13:3272–3281;1993.
Jeang K-T, Chun R, Lin NH, Gatignol A, Glabe CG, Fan H. In vitro and in vivo binding of human immunodeficiency virus type 1 Tat protein and Sp1 transcription factor. J Virol 67;6224–6233;1993.
Joel P, Shao W, Pratt K. A nuclear protein with enhanced binding to methylated Sp1 sites in the AIDS virus promoter. Nucleic Acids Res 21:5786–5793;1993.
Jones KA, Kadonaga JT, Luciw PA, Tjian R. Activation of the AIDS retrovirus promoter by the cellular transcription factor, Sp1. Science 232:755–759;1986.
Jost J-P, Hofsteenge J. The repressor MDBP-2 is a member of the histone H1 family that binds preferentially in vitro and in vivo to methylated nonspecific DNA sequences. Proc Natl Acad Sci USA 89:9499–9503;1992.
Levine A, Cantoni GL, Razin A. Methylation in the preinitiation domain suppresses gene transcription by an indirect mechanism. Proc Natl Acad Sci USA 89:10119–10123;1992.
Lewis JD, Meehan RR, Henzel WJ, Maurer-Fogy I, Jepesen P, Klein F, Bird A. Purification, sequence, and cellular localization of a novel chromosomal protein that binds to methylated DNA. Cell 69:905–914;1992.
Meehan RR, Lewis J, Bird AP. Characterization of MeCP2, a vertebrate DNA binding protein with affinity for methylated DNA. Nucl Acids Res 20:5085–5092;1992.
Meehan RR, Lewis JD, McKay S, Kleiner EL, Bird AP. Identification of a mammalian protein that binds specifically to DNA containing methylated CpGs. Cell 58:499–507;1989.
Pawlak A, Bryans M, Jost J. An avian 40 KDa nucleoprotein binds preferentially to a promoter sequence containing one single pair of methylated CpG. Nucl Acids Res 19:1029–1034;1991.
Sambrook J, Fritsch EF, Maniatis T. Molecular Cloning: a Laboratory Manual. 2nd edition. Cold Spring Harbor Laboratory Press, Cold Spring Harbor, 1989.
Supaker PC, Weist D, Zhang D, Inamdar N, Zhang XY, Khan R, Ehrlich KC, Ehrlich M. Methylated DNA-binding protein is present in various mammalian cell types. Nucleic Acids Res 16:8029–8046;1988.
Volpe P, Iacovacci P, Butler RH, Eremenko T. 5-methylcytosine in genes with methylation-dependent regulation. FEBS Lett 329:233–237;1993.
Zhang XY, Asiedu CK, Supakar PC, Khan R, Ehrlich KE, Ehrlich M. Binding sites in mammalian genes and viral gene regulatory regions recognized by methylated DNA binding protein. Nucleic Acids Res 18:6253–6260;1990.
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Shao, W. Characterization of HMBP-2, a DNA-binding protein that binds to HIV-1 LTR when only one of the three Sp1 sites is methylated. J Biomed Sci 4, 39–46 (1997). https://doi.org/10.1007/BF02255592
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DOI: https://doi.org/10.1007/BF02255592