Targeted derepression of the human immunodeficiency virus type 1 long terminal repeat by pyrrole-imidazole polyamides.
The host factor LSF represses the human immunodeficiency virus type 1 long terminal repeat (LTR) by mediating recruitment of histone deacetylase. We show that pyrrole-imidazole polyamides targeted to the LTR can specifically block LSF binding both in vitro and within cells via direct access to chromatin, resulting in increased LTR expression.
Coull
Jason J
JJ
Division of Infectious Diseases, Department of Medicine, University of Texas Southwestern Medical Center at Dallas, Dallas, Texas 75390, USA.
He
Guocheng
G
Melander
Christian
C
Rucker
Victor C
VC
Dervan
Peter B
PB
Margolis
David M
DM
D001483:Base Sequence; D002460:Cell Line; D004279:DNA, Viral / Q000235:genetics; D004268:DNA-Binding Proteins / Q000378:metabolism; D050981:Erythroid-Specific DNA-Binding Factors; D015870:Gene Expression / Q000187:drug effects; D005814:Genes, Viral / Q000187:drug effects; D015658:HIV Infections / Q000235:genetics / Q000378:metabolism / Q000821:virology; D016325:HIV Long Terminal Repeat / Q000187:drug effects*; D015497:HIV-1 / Q000187:drug effects* / Q000235:genetics*; D006367:HeLa Cells; D006655:Histone Deacetylases / Q000378:metabolism; D006801:Humans; D007093:Imidazoles / Q000737:chemistry / Q000494:pharmacology; D066298:In Vitro Techniques; D008969:Molecular Sequence Data; D009757:Nylons / Q000737:chemistry / Q000494:pharmacology*; D011758:Pyrroles / Q000737:chemistry / Q000494:pharmacology; D016601:RNA-Binding Proteins; D014157:Transcription Factors / Q000378:metabolism
D004279:DNA, Viral; D004268:DNA-Binding Proteins; D050981:Erythroid-Specific DNA-Binding Factors; D007093:Imidazoles; D009757:Nylons; D011758:Pyrroles; D016601:RNA-Binding Proteins; C501906:TFCP2 protein, human; D014157:Transcription Factors; D006655:Histone Deacetylases