Nucleic Acids Research, Vol 25, Issue 13 2589-2594, Copyright © 1997 by Oxford University Press
EE Turner, JM Rhee and LT Feldman
The restriction of herpes virus latency to mammalian sensory ganglia has
led to a search for tissue-specific regulatory molecules in these neurons
which alter viral gene expression. We have recently shown that the
POU-domain transcriptional regulator Brn-3.0 is abundantly expressed in the
adult trigeminal ganglion. To begin to examine the hypothesis that Brn-3.0
might participate in the regulation of the HSV life-cycle, we used Brn-3.0
POU-domain protein as an affinity matrix, and biochemically screened the
entire HSV genome for sites of Brn-3.0 binding. This screen identified
several sites of the form TA/TA A T N A N TA/T, which significantly do not
include the previously identified HSV octamer sequences. All of the
selected sites occur in the <25% of the HSV genome which has not been
assigned to open reading frames, suggesting that these sites may be
transcriptional regulatory elements recognized by Brn-3.0 or another
homeobox factor with similar DNA binding properties. However, these sites
do not interact with Brn-3.0 with sufficiently high affinity to directly
mediate transcriptional activation by Brn-3.0 alone in transfection assays.
The experiments described also provide an effective general method for
exhaustive screening of large viral genomes or sub-genomic fragments of
eukaryotic DNA for sites of interaction with specific transcription
factors.
ARTICLES
The POU-domain factor Brn-3.0 recognizes characteristic sites in the herpes simplex virus genome
Department of Psychiatry, University of California, San Diego, La Jolla, CA 92093-0603, USA. eturner@ucsd.edu
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