Promoter analysis – Bioinformatics Centre - University of Copenhagen

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Bioinformatics Centre > Research > Promoter analysis

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Promoter analysis:

An important aspect of understanding gene expression is tounderstand the transcriptional regulatory mechanisms of the genes.There are several layers of such mechanisms working on partiallydifferent scales :

  • Epigenetic and or chromosomal events that make DNA accessible
  • Binding of proteins to cis-regulatory elements, which can function as positive or negative regulators
  • Assembly and initiation of the transcriptional machinery at core promoters

In the promoter group we are developing models for these processes,in order to both predict the associated events and, even moreimportantly, to understand the processes. To this end we use bothadvanced machine learning methods and statistical analyses on novelhigh-throughput genomics data.  A unique strength in the group is that wecover the whole area from theoretical modeling, including machine learning,  to hands-on analysis andinterpretation of large sets of genomics data.


Some images relating to various aspects of our work - from left to right:

  • Left: Heatmap showing densities of predicted transcription factor binding sites in six groups of chp-chip experiments (combinations of estrogen receptor alpha and beta with or without expression of estrogen receptor beta). Note that the estrogen-alfa specific regions have different denisties than those that bind estrogen receptor beta. From  Liu Y, Gao H, Marstrand T, Ström A, Valen E, Sandelin A, Gustafson JÅ, Dahlman-Wright K: The genome landscape of ERα-  and ERβ-binding DNA regions; overlaps and distinctive features of binding sites for the two estrogen receptors. PNAS 2008, Accepted.
  • Middle: Over-represented k-mers (DNA "words") and their position relative to strong transcription start sites, using novel CAGE data. This was later used to define a code for transcription initiation. The image is a zoom-in of a figure in Frith MC, Valen E, Krogh A, Hayashizaki Y, Carninci P, Sandelin A: A code for transcription initiation in mammalian genomes. Genome Res 2008, 18(1):1-12.
  • Right: Relative densities of transcription initaition events in first, inner and last exons. In first exons, we see a much larger density in the 5' region, which is expected. in inner exons, the distribution is more or less flat, but in last exons there  is a n over-representation in the last 20%, often the UTR.  These are probably functional transcripts that are not regulated as the "home" gene. This is one of our contributions to The FANTOM consortium: The transcriptional landscape of the mammalian genome. Science 2005, 309(5740):1559-1563.

 

Selected publications

The following two reviews cover part of our focus areas:  

  • Sandelin A, Carninci P, Lenhard B, Ponjavic J, Hayashizaki Y, Hume DA: Mammalian RNA polymerase II core promoters: insights from genome-wide studies. Nat Rev Genet 2007, 8(6):424-436.
  • Wasserman WW, Sandelin A. Applied bioinformatics for the identification of regulatory elements.Nat Rev Genet. 2004 Apr;5(4):276-87.

 

2008 

  • Kawaji H, Nakamura M, Takahashi Y, Sandelin A, Katayama S, Fukuda S, Daub CO, Kai C, Kawai J, Yasuda J, Carninci P, Hayashizaki Y:Hidden layers of human small RNAs. BMC Genomics. 2008 Apr 10;9(1):157
  • Liu Y, Gao H, Marstrand T, Ström A, Valen E, Sandelin A, Gustafson JÅ, Dahlman-Wright K: The genome landscape of ERα-  and ERβ-binding DNA regions; overlaps and distinctive features of binding sites for the two estrogen receptors. Proc Natl Acad Sci U S A. 2008 Feb 19;105(7):2604-9
  • Marstrand TT, Frellsen J, Moltke I, Thiim M, Valen E, Retelska D, Krogh A Asap: a framework for over-representation statistics for transcription factor binding sites.PLoS ONE. 2008 Feb 20;3(2):e1623.
  • Frith MC, Valen E, Krogh A, Hayashizaki Y, Carninci P, Sandelin A: A code for transcription initiation in mammalian genomes. Genome Res 2008, 18(1):1-12.
  • Bryne JC, Valen E, Tang MH, Marstrand T, Winther O, da Piedade I, Krogh A, Lenhard B, Sandelin A: JASPAR, the open access database of transcription factor-binding profiles: new content and tools in the 2008 update. Nucleic Acids Res. 2008 Jan;36(Database issue):D102-6.
  • Gao H, Fält S, Sandelin A, Gustafsson JA, Dahlman-Wright K. Genome-wide identification of estrogen receptor alpha-binding sites in mouse liver. Mol Endocrinol. 2008 Jan;22(1):10-22.

2007

  • The ENCODE Consortium: Identification and analysis of functional elements in 1% of the human genome by the ENCODE pilot project. Nature 2007, 447(7146):799-816.
  • Hansen TV, Borup R, Marstrand T, Rehfeld JF, Nielsen FC. Cholecystokinin-2 receptor mediated gene expression in neuronal PC12 cells.J Neurochem. 2007 Nov 17; [Epub ahead of print]
  • Sandelin A, Carninci P, Lenhard B, Ponjavic J, Hayashizaki Y, Hume DA: Mammalian RNA polymerase II core promoters: insights from genome-wide studies. Nat Rev Genet 2007, 8(6):424-436.

    2006

    • Kawaji H, Frith MC, Katayama S, Sandelin A, Kai C, Kawai J, Carninci P, Hayashizaki Y. Dynamic usage of transcription start sites within core promoters. Genome Biol. 2006;7(12):R118.

     

    PIs

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    Master students

    • Xiaobei Zhao