Gene Expression and Transcriptional Regulation

Abstract To ensure that the subsequent discussions of transcriptional regulation and molecular pathophysiology will be accessible to those not well versed in this literature, a brief overview will be presented first. Whereas molecular geneticists may wish to forgo this introductory course and proceed directly to the second half of the chapter (beginning with “The Transcription Initiation Complex”), the uninitiated should not do so until the definitions and organizing principles in the first three sections have been thoroughly digested. If additional introductory material is needed, a basic textbook in molecular biology should be consulted (e.g., Lewin, 1997). The most basic (and most misused) terminology in molecular genetics relates to gene structure (Fig. 1.1). For the purposes of this text a gene will be defined as a continuous, uninterrupted, chromosomal (genomic) DNA sequence that constitutes one (or more) transcription unit(s) from the (5’-most) transcription initiation site to the sequence corresponding to the (3’-most) polyadenylation site found in the transcribed messenger RNA(s) (mRNA). This somewhat cumbersome definition takes into ac count genes with multiple transcription initiation and polyadenylation sites. Sequences flanking the transcription unit(s) are referred to as 5’ and 3’-flanking sequences (5’-FS and 3’-FS). Because many cis-acting transcriptional regulatory elements are located within flanking sequences, they are not formally considered part of the gene proper.