IMI Interdisciplinary Mathematics InstituteCollege of Arts and Sciences

Binding site sequence does not determine function- but position helps

  • April 6, 2009
  • 11 a.m.
  • Sumwalt 102

Abstract

The natural prejudice when associating a piece of DNA with its biological function is to regard the DNA sequence as "having" some intrinsic biological function. The TRANSFAC database of transcription factor binding sites (TFBSs), e.g., displays this prejudice: it gives various TFBS sequences, along with their "functions". Against the backdrop of that prejudice, this talk describes an extraordinary finding: the regulatory function of a DNA sequence can vary with its position relative to a genomic landmark. Such a conclusion would be inaccessible to methods based purely on sequence, but not to techniques based on "positional regulomics", which exploits a multiple sequence alignment anchored on a specific genomic landmark. Our conclusion is based on a multiple alignment of proximal promoters anchored on experimentally determined transcription start sites (TSSs). Our anchored alignment indicated many 8-letter words fell into statistically significant clusters. Of these clusters, 78 specific words clustered in two or three different positions relative to the TSS. Often, the groups of genes corresponding to different clusters of the same word had diverse functions, e.g., activation or repression in different tissues. Different clusters of the same word likely reflect a phenomenon of "positional regulation", i.e., a word's regulatory function can vary with its position relative to a genomic landmark.

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