A novel sequence-specific DNA-binding protein, LCP-1, interacts with single-stranded DNA and differentially regulates early gene expression of the human neurotropic JC virus.

Abstract:

:We have identified a novel brain-derived single-stranded-DNA-binding protein that interacts with a region of the human neurotropic JC virus enhancer designated the lytic control element (LCE). This nuclear factor, LCP-1 (for lytic control element-binding protein 1), specifically recognizes the LCE, as determined by gel retardation assays. Alkylation interference showed that specific nucleotides within the LCE were contacted by LCP-1. Subsequent experiments revealed that point mutations within the LCE differentially affected LCP-1 binding. UV cross-linking and competition analysis suggested that the LCP-1 DNA-protein complexes were 50 to 52 and 100 to 120 kDa in size. Promoter mutations that affected LCP-1 binding reduced early mRNA transcription during the early phase of the lytic cycle. However, upon DNA replication in the presence of JC virus T antigen, when early mRNA initiation shifts to new locations indicative of the late phase, the LCP-1 mutations had no effect. We suggest that the JC virus early transcription unit is differentially regulated by LCP-1 prior to but not after DNA replication, suggesting a novel mechanism by which DNA structure regulates eukaryotic gene expression.

journal_name

J Virol

journal_title

Journal of virology

authors

Tada H,Khalili K

doi

10.1128/JVI.66.12.6885-6892.1992

subject

Has Abstract

pub_date

1992-12-01 00:00:00

pages

6885-92

issue

12

eissn

0022-538X

issn

1098-5514

journal_volume

66

pub_type

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