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Mechanisms of transcription: the eukaryotic pre-initiation complex
A selection of talks on Genetics & Epigenetics
Genetic counseling: preconception, prenatal, perinatal
- Prof. Aubrey Milunsky
- Tufts University School of Medicine, USA
Recent advances in the development of gene delivery technologies
- Dr. Takis Athanasopoulos
- GSK, UK
Mechanisms of Transcription; The Eukaryotic Pre-initiation Complex by Michael Hampsey.
In this talk, I focus on basic aspects of transcription, specifically transcription of eukaryotic class II genes, those transcribed by RNA polymerase II. I want to start by reminding you that transcription in eukaryotic cells is catalyzed by three distinct RNA polymerases, Pol I, Pol II, and Pol III. Pol I is dedicated to the synthesis of ribosomal RNAs, except the smallest of them, 5S RNA. Pol II transcribes protein encoding genes to yield messenger RNA as well as a few small nuclear RNAs, and Pol III synthesizes transfer RNAs, 5S ribosomal RNA, and also a few small nuclear RNAs. Whereas only messenger RNA is translated to yield protein, the ribosomal and transfer RNAs are also directly involved in protein synthesis by the ribosome.
In 2001, the complete DNA sequence of the human genome was published, revealing approximately 30,000 protein encoding genes. This was an extraordinary achievement, but like so many scientific milestones raised as many questions as were answered. Notable are the questions of how these 30,000 genes are expressed to affect cell growth and differentiation and how expression of these genes is regulated.
There are interesting implications regarding transcription mechanisms inherent in the DNA sequences of eukaryotic genomes. As I just mentioned, there are about 30,000 genes in the human genome and an estimated 3,000 Pol II transcription factors. On the other hand, the DNA sequence of the yeast genome revealed about 6,000 genes, but fewer than 300 transcription factors. Accordingly, there is less than one transcription factor for every 20 yeast genes compared to about one for every 10 genes in human cells. As you will see in the context of the Pol II enhanceosome, this two fold increase in the number of transcription factors per gene, affords the potential for an enormous increase in transcriptional regulatory complexity and is likely to underlie at least in part the dramatic expansion in organismal complexity from yeast to man. This talk addresses several fundamental questions regarding Pol II transcription.