Advances in high throughput sequencing technology have enabled analysis of transcription factor (TF) binding sites in genome scale. Analysis of linear profiles of transcription factor binding on eukaryotic chromosomes is a complex bioinfomatics task. Studying of 3D chromosomal organization of transcription regulation in genome is another challenging problem. Experiments on in situ fluorescence suggest that transcription is not evenly distributed, but rather concentrated within large discrete foci in mammalian nuclei, raising the possibility that genes are organized into “transcription factories” containing RNA polymerase II and other protein components. Chromosome Conformation Capture (3C) and similar techniques (4C, 5C, Hi-C) along with traditional in situ techniques have demonstrated that chromatin interactions are not randomly distribute in the genome, but rather form interaction clusters that can regulate transcriptional and epigenetic states. Using genome-wide Chromatin Interaction Analysis with Paired-End-Tag sequencing (ChIA-PET), we mapped long-range chromatin interactions associated with RNA polymerase II in human cells and uncovered widespread promoter-centered interactions [1]. These interactions could be further aggregated into higher-order clusters, in which proximal and distant genes are engaged through promoter-promoter interactions. We have compared location of chromosome interacting sites and available data on gene annotation, location of transcription regulatory regions and histone modifications. Same approach was used for ER-mediated interactome [2]. We show that most genes with promoter-promoter interactions are highly active and could transcribe cooperatively, and that some interacting promoters could influence each other, implying combinatorial complexity of transcriptional controls. Integration of such genome-wide data with ChIP-seq transcriptional profiles from ENCODE project and RNA-seq transcriptome profiles challenges new tasks for genome informatics. Recent application of genome architecture investigation experiments is done at ICG by Hi-C method in mouse fibroblasts. Preliminary results confirm conservation of genome structure presented by Hi-C experiments in mouse.

References:
1. G. Li et al. (2012) Extensive promoter-centered chromatin interactions provide a topological basis for transcription regulation, Cell, 148(1-2):84-98.
2. M.J. Fullwood et al. (2009) An oestrogen-receptor-alpha-bound human chromatin interactome. Nature, 462(7269): 58-64.