The yin and yang of chromatin spatial organization

Long-range chromatin interactions can occur over many megabases, either between regions of the same chromosome (cis) or between different chromosomes (trans). Many chromatin clustering events involve preferential interactions between genomic loci and are cell type specific, indicating a functional role of genome organization in regulating gene expression. Many mechanisms are involved in establishing global organization, including transcription by specific sets of transcription factors or gene repression among similar epigenetically marked domains. Here, we discuss several examples of specific spatial organization patterns from transcriptionally active and silent chromatin and the potential mechanisms involved in their establishment.A growing number of specific long-range chromatin interactions have been identified, indicating that the three-dimensional organization of chromatin within the nucleus is not random. These interactions have been found using tools such as RNA and DNA fluorescence in situ hybridization (FISH) and the chromatin proximity-ligation assay chromosome conformation capture (3C) and its derivatives [1]. In 3C, genomic regions in spatial proximity are cross-linked and digested with a restriction enzyme while in the nucleus. After nuclear lysis, the cross-linked chromatin complexes are diluted and ligated such that ends of restriction fragments in the same cross-linked complex form novel ligation junctions that can be detected by various methods. Numerous studies using these tools have shown that the three-dimensional organization of chromatin within the nucleus is not random. One of the best known and studied long-range interactions occurs between the erythroid-specific β-globin gene and its long-range enhancer, the distal locus control region (LCR). The mammalian β-globin LCR consists of five DNase I hypersensitive sites (HS1-HS5) distributed over 15 kb, located approximately 50 kb upstream of the β-globin gene. The LCR regulates β-globin gene tran