Understanding the mechanisms underlying the initiation and regulation of transcription remains one of the most fundamental questions in biology. Much of what we know about the transcription process was inferred from experiments on a handful of genes. As these experiments are not realistically scalable, corresponding computational methods building on these findings have emerged; however, these are not accurate enough for annotation of genomes. The limitations reflect that we have no accurate universal model describing transcription initiation; to a large extent, our understanding is based on case stories. Recently, high-throughput methods have been developed to chart the TSS landscape with nucleotide resolution. Using these data, I have dissected promoters at nucleotide level and found patterns that explain the transcription initiation rate for individual nucleotides. The objective for this work is to extend this to the first universal model for how cells select core promoters and associated TSSs. This will have two counterparts: i)prediction of TSSs from DNA sequence given a region of accessible DNA, and ii)prediction of DNA accessibility based on DNA sequences and dynamic epigenetic factors. Such a model will be a corner stone of future experimental and computational transcriptome and gene regulation studies.
Field of science
- /natural sciences/biological sciences/genetics and heredity/dna
- /natural sciences/biological sciences/genetics and heredity/nucleotide
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