The molecular basis of eukaryotic transcription
- Stanford University School of Medicine, Stanford, CA 94305-5400
I am deeply grateful for the honor bestowed on me by the Nobel Committee for Chemistry and the Royal Swedish Academy of Sciences. It is an honor I share with my collaborators. It is also recognition of the many who have contributed over the past quarter century to the study of transcription.
The Nucleosome
My own involvement in studies of transcription began with the discovery of the nucleosome, the basic unit of DNA coiling in eukaryote chromosomes (1). X-ray studies and protein chemistry led me to propose the wrapping of DNA around a set of eight histone molecules in the nucleosome (Fig. 1). Some years later, Yahli Lorch and I found that this wrapping of DNA prevents the initiation of transcription in vitro (2). Michael Grunstein and colleagues showed nucleosomes interfere with transcription in vivo (3). The nucleosome serves as a general gene repressor. It assures the inactivity of all of the many thousands of genes in eukaryotic cells except those whose transcription is brought about by specific positive regulatory mechanisms. What are these positive regulatory mechanisms? How is repression by the nucleosome overcome for transcription? Our recent work has shown that promoter chromatin is transformed from a static to a dynamic state upon gene activation (4). Nucleosomes are rapidly removed and reassembled in the activated state. Promoter DNA is made transiently available for interaction with the transcription machinery.
The nucleosome, the fundamental particle of the eukaryote chromosome. Schematic shows the coiling of DNA around a set of eight histones in the nucleosome, the further coiling in condensed (transcriptionally inactive) chromatin, and uncoiling for interaction with the RNA polymerase II (pol II) transcription machinery.
RNA Polymerase II (Pol II) Transcription
Our studies have focused on the RNA pol II transcription machinery. Pol II is responsible for all messenger RNA synthesis in eukaryotes. As the first step in gene …
*E-mail: kornberg{at}stanford.edu
