CCAAT/enhancer binding proteins are not required for HIV-1 entry but regulate proviral transcription by recruiting coactivators to the long-terminal repeat in monocytic cells.
CCAAT/enhancer binding proteins (C/EBP) have been shown to be required for HIV-1 transcription and replication in macrophages. However, whether these transcription factors influence the ability of virus to establish infection by altering cytokine or receptor expression or primarily regulate HIV-1 transcription has not been determined. By inhibiting endogenous C/EBP activity with a dominant-negative protein, we demonstrate that functional C/EBPs are not required for HIV-1 infection and that these factors influence replication by a transcriptional mechanism. C/EBPbeta recruits coactivators to the HIV-1 long-terminal repeat (LTR) and physically interacts with histone acetyltransferase (HAT) complexes, suggesting that C/EBPs participate in remodeling the chromatin organization of the HIV-1 provirus. Furthermore, overexpression of a C/EBP dominant-negative inhibits displacement of nucleosomes located at the HIV-1 transcriptional start site. These results provide insight into the general mechanisms by which C/EBPs regulate macrophage-restricted HIV-1 transcription.
Lee
Eileen S
ES
Graduate Program in Biochemistry, Microbiology, and Molecular Biology, The Pennsylvania State University, University Park 16802, USA.
Sarma
Deba
D
Zhou
Huiyu
H
Henderson
Andrew J
AJ
D000123:Acetyltransferases / Q000378:metabolism; D022782:CCAAT-Enhancer-Binding Protein-beta / Q000378:metabolism; D022762:CCAAT-Enhancer-Binding Proteins / Q000378:metabolism*; D002843:Chromatin / Q000201:enzymology / Q000235:genetics; D015658:HIV Infections / Q000097:blood / Q000821:virology*; D016325:HIV Long Terminal Repeat / Q000235:genetics; D015497:HIV-1 / Q000235:genetics / Q000502:physiology*; D051548:Histone Acetyltransferases; D006801:Humans; D009000:Monocytes / Q000821:virology*; D011485:Protein Binding; D011533:Proviruses / Q000235:genetics / Q000502:physiology*; D029701:Saccharomyces cerevisiae Proteins / Q000378:metabolism; D014158:Transcription, Genetic; D020298:U937 Cells; D014779:Virus Replication
D022782:CCAAT-Enhancer-Binding Protein-beta; D022762:CCAAT-Enhancer-Binding Proteins; D002843:Chromatin; D029701:Saccharomyces cerevisiae Proteins; D000123:Acetyltransferases; D051548:Histone Acetyltransferases