A code for transcription initiation in mammalian genomes

Frith, Martin C., Valen, Eivind, Krogh, Anders, Hayashizaki, Yoshihide, Carninci, Piero and Sandelin, Albin (2008) A code for transcription initiation in mammalian genomes. Genome Research, 18 1: 1-12.


Author Frith, Martin C.
Valen, Eivind
Krogh, Anders
Hayashizaki, Yoshihide
Carninci, Piero
Sandelin, Albin
Title A code for transcription initiation in mammalian genomes
Journal name Genome Research   Check publisher's open access policy
ISSN 1088-9051
Publication date 2008-01
Sub-type Article (original research)
DOI 10.1101/gr.6831208
Volume 18
Issue 1
Start page 1
End page 12
Total pages 12
Place of publication United States
Publisher Cold Spring Harbor Laboratory Press
Language eng
Formatted abstract Genome-wide detection of transcription start sites (TSSs) has revealed that RNA Polymerase II transcription initiates at millions of positions in mammalian genomes. Most core promoters do not have a single TSS, but an array of closely located TSSs with different rates of initiation. As a rule, genes have more than one such core promoter; however, defining the boundaries between core promoters is not trivial. These discoveries prompt a re-evaluation of our models for transcription initiation. We describe a new framework for understanding the organization of transcription initiation. We show that initiation events are clustered on the chromosomes at multiple scales-clusters within clusters-indicating multiple regulatory processes. Within the smallest of such clusters, which can be interpreted as core promoters, the local DNA sequence predicts the relative transcription start usage of each nucleotide with a remarkable 91% accuracy, implying the existence of a DNA code that determines TSS selection. Conversely, the total expression strength of such clusters is only partially determined by the local DNA sequence. Thus, the overall control of transcription can be understood as a combination of large- and small-scale effects; the selection of transcription start sites is largely governed by the local DNA sequence, whereas the transcriptional activity of a locus is regulated at a different level; it is affected by distal features or events such as enhancers and chromatin remodeling.
Keyword Polymerase-ii Transcription
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collection: Institute for Molecular Bioscience - Publications
 
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Created: Thu, 03 Sep 2009, 10:35:52 EST by Mr Andrew Martlew on behalf of Institute for Molecular Bioscience