GATA-2 and HNF-3β Regulate the Human Alcohol Dehydrogenase 1A ( ADH1A) Gene.

Autor: Dannenberg, Luke O., Hui-Ju Chen, Edenberg, Howard J.
Předmět:
Zdroj: DNA & Cell Biology; Sep2005, Vol. 24 Issue 9, p543-552, 10p
Abstrakt: In this paper, we have identified several distal cis-acting elements that contribute to the regulation and tissue- specificity of ADH1A, which encodes an alcohol dehydrogenase (ADH) that metabolizes ethanol. A negative element from bp –1873 to –1558, relative to the translational start site, decreased transcriptional activity to 52% in H4IIE-C3 cells and 70% in CV-1 cells. A positive element from bp –2459 to –2173 increased transcriptional activity twofold in H4IIE-C3 cells and 1.7-fold in CV-1 cells. Gel mobility shift and supershift assays demonstrated that GATA-2 bound a region within this positive element. A tissue-specific regulatory element from bp –6380 to –5403 increased transcription twofold in H4IIE-C3 cells while decreasing transcription to 86% in CV-1 cells. Within this tissue-specific fragment, the region from bp –5668 to –5403 increased transcription 1.7-fold in H4IIE-C3 cells and 1.3-fold in CV-1 cells. Hepatocyte nuclear factor-3β (HNF- 3β) bound a region of the tissue-specific element in CV-1 cells, but not in H4IIE-C3 cells. Positive regulation of the ADH1A gene may be influenced by GATA-2 binding, while differences in HNF-3β binding in cells/tissues may contribute to tissue specificity. [ABSTRACT FROM AUTHOR]
Databáze: Complementary Index