Sequence features that drive human promoter function and tissue specificity
AuthorsLandolin, Jane M.
Johnson, David S.
Trinklein, Nathan D.
Aldred, Shelley Force
Shulha, Hennady P.
Myers, Richard M.
UMass Chan AffiliationsProgram in Bioinformatics and Integrative Biology
Department of Biochemistry and Molecular Pharmacology
Hep G2 Cells
Hepatocyte Nuclear Factor 4
Promoter Regions, Genetic
Genetics and Genomics
MetadataShow full item record
AbstractPromoters are important regulatory elements that contain the necessary sequence features for cells to initiate transcription. To functionally characterize a large set of human promoters, we measured the transcriptional activities of 4575 putative promoters across eight cell lines using transient transfection reporter assays. In parallel, we measured gene expression in the same cell lines and observed a significant correlation between promoter activity and endogenous gene expression (r = 0.43). As transient transfection assays directly measure the promoting effect of a defined fragment of DNA sequence, decoupled from epigenetic, chromatin, or long-range regulatory effects, we sought to predict whether a promoter was active using sequence features alone. CG dinucleotide content was highly predictive of ubiquitous promoter activity, necessitating the separation of promoters into two groups: high CG promoters, mostly ubiquitously active, and low CG promoters, mostly cell line-specific. Computational models trained on the binding potential of transcriptional factor (TF) binding motifs could predict promoter activities in both high and low CG groups: average area under the receiver operating characteristic curve (AUC) of the models was 91% and exceeded the AUC of CG content by an average of 23%. Known relationships, for example, between HNF4A and hepatocytes, were recapitulated in the corresponding cell lines, in this case the liver-derived cell line HepG2. Half of the associations between tissue-specific TFs and cell line-specific promoters were new. Our study underscores the importance of collecting functional information from complementary assays and conditions to understand biology in a systematic framework.
SourceGenome Res. 2010 Jul;20(7):890-8. doi: 10.1101/gr.100370.109. Epub 2010 May 25. Link to article on publisher's site
Permanent Link to this Itemhttp://hdl.handle.net/20.500.14038/25892
Related ResourcesLink to Article in PubMed