Abstract
An application of machine learning algorithms enables prediction of the functional context of transcription factor binding sites in the human genome.
Highlights
Regulation of gene expression is accomplished through binding of transcription factors (TFs) to distinct regions of DNA (TF binding sites (TFBSs)), and, after anchoring at these sites, transmission of the regulatory signal to the basal transcription complex
Repeats in HNF4 binding sites It is generally accepted that HNF4 regulates gene expression by binding to direct repeat motifs of the RG(G/T)TCA sequence separated by one nucleotide (direct repeat (DR)1) [13]
We found that the DR1 repeat structure is clearly seen in the general consensus and in the full positional weight matrix, actual genomic sites often can be characterized by more complicated structures
Summary
Regulation of gene expression is accomplished through binding of transcription factors (TFs) to distinct regions of DNA (TF binding sites (TFBSs)), and, after anchoring at these sites, transmission of the regulatory signal to the basal transcription complex. Regions around TFBSs can be interrogated with regards to binding and interaction with other TFs (so-called composite modules) as well as local sequence properties that favor recruitment of TFs, bending and looping of DNA and nucleosome positioning Some of these TFs are specific for a particular tissue, a definite stage of development, or a given extracellular signal, but most TFs are involved in gene regulation under a rather wide spectrum of cellular conditions. There may be several different types of CMs located in the regulatory region of one gene, which may be distant from each other (for example, liver- and muscle-specific enhancers of one gene) or overlapping Taking this into account, it becomes more and more evident that the 'local sequence context' in the vicinity of the TFBS, as well as 'global context' of the whole promoter/enhancer where the TF site is located, influences binding and functioning of the corresponding TF. For the TF family of nuclear receptors (to which hepatocyte nuclear factor (HNF) factors belong) there is experimental evidence showing clear dependence between functioning of HNF4
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