(Hypertension. 1996;27:980-1008.)
© 1996 American Heart Association, Inc.
Articles |
Transcriptional Regulation of the Genes Involved in Lipoprotein Transport
The Role of Proximal Promoters and Long-range Regulatory Elements and Factors in Apolipoprotein Gene Regulation
From the Section of Molecular Genetics, Boston (Mass) University Medical Center (D.K., M.L., V.Z.), and the University of Crete Medical School and Institute of Molecular Biology and Biotechnology of Crete (Greece) (D.K., I.T., V.Z.).
Correspondence to D. Kardassis, Section of Molecular Genetics, Boston University Medical Center, 700 Albany St, Boston, MA 02118-2394.
Key Words: apolipoproteins • genes, regulator • gene expression regulation • transcription factors • eukaryotic genes
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Introduction |
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The transcription of eukaryotic genes is a complex biological event involving numerous proteins—including RNA polymerase II, the proteins of the basal transcription initiation complex, and a variety of promoter- and enhancer-specific transcription factors—and requiring an ATP-dependent activation step.1 2 3 4 5 6 7 8 9 10 11 12 The regulation of transcription is responsible for the tissue-specific gene expression as well as gene expression during differentiation and development and in response to intracellular and extracellular stimuli such as hormones and metabolites.
Numerous studies have established that a precise array of regulatory elements exists in each promoter/enhancer and these elements are occupied by transcription factors. It has been proposed that this promoter/enhancer-specific arrangement of factors permits the formation of stereospecific DNA-protein complexes. These complexes may directly or indirectly interact with the basal transcription system, thus leading to the transcriptional activation of the target gene.8 13
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Methodologies Used for Study of Transcriptional Regulation of Genes |
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Several experimental advances have facilitated the study of eukaryotic promoters and have led to the identification and characterization of several eukaryotic transcription factors. These include the following: (1) Definition of the long-range regulatory elements that confer tissue specificity or developmentally regulated expression. This analysis utilizes transgenic mouse technologies.14 15 (2) Definition of the promoter region a few kilobases upstream of the transcription initiation site necessary for gene transcription. This analysis monitors the expression of a reporter gene under the control of normal and mutated promoters after transfection of cell cultures. (3) Identification of the different factors that bind to a specific promoter region and definition of their binding sites on the DNA. For this purpose, several techniques are
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