Molecular Systems Biology, 2006, msb4100054

Từ Thư viện Khoa học VLOS
Bước tới: chuyển hướng, tìm kiếm
Các nguyên tắc điều khiển phiên mã ở genome sinh vật nhân chuẩn
Deciphering principles of transcription regulation in eukaryotic genomes
 Tạp chí Molecular Systems Biology 2006 18 April 2006; ():msb4100054
 Tác giả   Dat H Nguyen1 và Patrik D'haeseleer1
 Nơi thực hiện   Department of Genetics, Harvard Medical School, Boston, MA, USA
 Từ khóa   Computational methods, Transcription


Transcription regulation has been responsible for organismal complexity and diversity in the course of biological evolution and adaptation, and it is determined largely by the context-dependent behavior of cis-regulatory elements (CREs). Therefore, understanding principles underlying CRE behavior in regulating transcription constitutes a fundamental objective of quantitative biology, yet these remain poorly understood. Here we present a deterministic mathematical strategy, the motif expression decomposition (MED) method, for deriving principles of transcription regulation at the single-gene resolution level. MED operates on all genes in a genome without requiring any a priori knowledge of gene cluster membership, or manual tuning of parameters. Applying MED to Saccharomyces cerevisiae transcriptional networks, we identified four functions describing four different ways that CREs can quantitatively affect gene expression levels. These functions, three of which have extrema in different positions in the gene promoter (short-, mid-, and long-range) whereas the other depends on the motif orientation, are validated by expression data. We illustrate how nature could use these principles as an additional dimension to amplify the combinatorial power of a small set of CREs in regulating transcription.

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