TY - JOUR
T1 - DNase I hypersensitive site maps to the HBV enhancer
AU - El-Ghor, M. Akmal A.
AU - Burk, Robert D.
N1 - Funding Information:
This work was supported by Public Health Service Grant CA45476 from the National Cancer Institute, Grant No. JFRA-172 from the American Cancer Society, and a grant from the Sinsheimer Foundation. M. A. A. El-Ghor was supported by a Peace Fellowship from the Amideast program for Egypt and the Camp David Institute for International Health. We thank David A. Shafritz and Charles E. Rogler for critically reading the manuscript.
PY - 1989/10
Y1 - 1989/10
N2 - Two lines of HBV transgenic mice (derived from G7 and G26) have been produced, each of which contains a unique locus of HBV DNA and expresses 2.1-kb HBsAg transcripts preferentially in liver and kidney tissues. To investigate the regulation of HBV expression in these mice, we have examined the state of methylation and the chromatin structure in and around the HBV sequences in tissues with and without HBV gene expression. Hypomethylation of Hpall and Hhal sites in and around the HBV sequences strongly correlated with HBV gene expression, although it was clearly not sufficient for HBV expression. Alterations in chromatin configuration were detected by DNase I digestion which identified a major hypersensitive site (HS) in liver and kidney tissue. By restriction enzyme mapping and indirect end-labeling, the HS was localized to the region of the HBV enhancer in both lines of HBV transgenics. The presence of this DNase I hypersensitive site was necessary but not sufficient for HBV expression, since it was also detected in tissues not expressing HBV. An additional DNase I hypersensitive site was mapped to the core promoter region of the G7 transgene in liver and kidney tissue but not in G26 tissues. The identification of a DNase I hypersensitive site mapping to the HBV enhancer region supports the notion that this region can interact with cellular proteins and is involved in the regulation of viral gene transcription in vivo.
AB - Two lines of HBV transgenic mice (derived from G7 and G26) have been produced, each of which contains a unique locus of HBV DNA and expresses 2.1-kb HBsAg transcripts preferentially in liver and kidney tissues. To investigate the regulation of HBV expression in these mice, we have examined the state of methylation and the chromatin structure in and around the HBV sequences in tissues with and without HBV gene expression. Hypomethylation of Hpall and Hhal sites in and around the HBV sequences strongly correlated with HBV gene expression, although it was clearly not sufficient for HBV expression. Alterations in chromatin configuration were detected by DNase I digestion which identified a major hypersensitive site (HS) in liver and kidney tissue. By restriction enzyme mapping and indirect end-labeling, the HS was localized to the region of the HBV enhancer in both lines of HBV transgenics. The presence of this DNase I hypersensitive site was necessary but not sufficient for HBV expression, since it was also detected in tissues not expressing HBV. An additional DNase I hypersensitive site was mapped to the core promoter region of the G7 transgene in liver and kidney tissue but not in G26 tissues. The identification of a DNase I hypersensitive site mapping to the HBV enhancer region supports the notion that this region can interact with cellular proteins and is involved in the regulation of viral gene transcription in vivo.
UR - http://www.scopus.com/inward/record.url?scp=0024396853&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0024396853&partnerID=8YFLogxK
U2 - 10.1016/0042-6822(89)90190-6
DO - 10.1016/0042-6822(89)90190-6
M3 - Article
C2 - 2800333
AN - SCOPUS:0024396853
SN - 0042-6822
VL - 172
SP - 478
EP - 488
JO - Virology
JF - Virology
IS - 2
ER -