A position-dependent silencer plays a major role in repressing. alpha. -fetoprotein expression in human hepatoma
Journal Article
·
· Molecular and Cellular Biology; (United States)
- Univ. of Calgary, Alberta (Canada)
A large percentage of human hepatomas produce {alpha}-fetoprotein (AFP), but the levels of AFP expression vary greatly among hepatomas. To understand the molecular basis for this variation. The authors analyzed transcriptional regulatory activities associated with the 5{prime}-flanking region of the AFP gene in two human hepatoma cell lines, HuH-7 and huH-1/cl-2, which produce a high and a low level of AFP, respectively. They found that the low level of AFP production in huH-1/cl-2 is due to the action of at least two silencer regions located between the enhancer and the promoter of the AFP gene. In contrast, no silencer activity is expressed in HuH-7. They identified 5{prime}-CTTCATAACTAATACTT-3{prime} to be a core sequence responsible for the negative regulatory activity. This sequence is repeated four times in a strong, distal silencer region, Sd, whereas one copy is present in a weak, proximal silencer region, Sp. The silencer reduces transcriptional initiation by blocking enhancer activation of the AFP promoter in a position-dependent manner. The silencer functions in the presence of positive transcription factors and may play a key role in developmental repression as well as variable expression of the AFP gene in hepatomas.
- OSTI ID:
- 5144644
- Journal Information:
- Molecular and Cellular Biology; (United States), Journal Name: Molecular and Cellular Biology; (United States) Vol. 11:12; ISSN MCEBD; ISSN 0270-7306
- Country of Publication:
- United States
- Language:
- English
Similar Records
Enhancer and promoter elements directing activation and glucocorticoid repression of the. cap alpha. /sub 1/-fetoprotein gene in hepatocytes
Expression of human. alpha. -fetoprotein in yeast
Repression of the Drosophila proliferating-cell nuclear antigen gene promoter by zerknuellt protein
Journal Article
·
Thu Mar 31 23:00:00 EST 1988
· Mol. Cell. Biol.; (United States)
·
OSTI ID:7192090
Expression of human. alpha. -fetoprotein in yeast
Journal Article
·
Sun Dec 31 23:00:00 EST 1989
· Life Sciences; (USA)
·
OSTI ID:6705168
Repression of the Drosophila proliferating-cell nuclear antigen gene promoter by zerknuellt protein
Journal Article
·
Tue Oct 01 00:00:00 EDT 1991
· Molecular and Cellular Biology; (United States)
·
OSTI ID:5118548