Nuclear factor I revealed as family of promoter binding transcription activators
- Equal contributors
1 Institute of Biotechnology, University of Lausanne, and Center for Biotechnology of the University of Lausanne and École Polytechnique Fédérale de Lausanne, CH-1015 Lausanne, Switzerland
2 Software Examination and Certification Laboratory, Faculty of Mathematics, University of Belgrade, 11000 Belgrade, Serbia
3 Swiss Institute for Experimental Cancer Research, École Polytechnique Fédérale de Lausanne, CH-1015 Lausanne, Switzerland
4 Swiss Tropical and Public Health Institute, Socinstrasse 57, P.O. Box, CH-4002 Basel, Switzerland
5 Universität Basel, Petersplatz 1, CH-4003 Basel, Switzerland
6 Swiss Institute of Bioinformatics, EPFL SV ISREC, AAB 0 09 (Bâtiment AAB), Station 15, CH-1015 Lausanne, Switzerland
7 Department of Mathematics, University of Fribourg, CH-1700 Fribourg, Switzerland
BMC Genomics 2011, 12:181 doi:10.1186/1471-2164-12-181Published: 7 April 2011
Multiplex experimental assays coupled to computational predictions are being increasingly employed for the simultaneous analysis of many specimens at the genome scale, which quickly generates very large amounts of data. However, inferring valuable biological information from the comparisons of very large genomic datasets still represents an enormous challenge.
As a study model, we chose the NFI/CTF family of mammalian transcription factors and we compared the results obtained from a genome-wide study of its binding sites with chromatin structure assays, gene expression microarray data, and in silico binding site predictions. We found that NFI/CTF family members preferentially bind their DNA target sites when they are located around transcription start sites when compared to control datasets generated from the random subsampling of the complete set of NFI binding sites. NFI proteins preferably associate with the upstream regions of genes that are highly expressed and that are enriched in active chromatin modifications such as H3K4me3 and H3K36me3. We postulate that this is a causal association and that NFI proteins mainly act as activators of transcription. This was documented for one member of the family (NFI-C), which revealed as a more potent gene activator than repressor in global gene expression analysis. Interestingly, we also discovered the association of NFI with the tri-methylation of lysine 9 of histone H3, a chromatin marker previously associated with the protection against silencing of telomeric genes by NFI.
Taken together, we illustrate approaches that can be taken to analyze large genomic data, and provide evidence that NFI family members may act in conjunction with specific chromatin modifications to activate gene expression.