Beyond the Sequence: Cellular Organization of Genome Function Tom Misteli  Cell  Volume 128, Issue 4, Pages 787-800 (February 2007) DOI: 10.1016/j.cell.2007.01.028 Copyright © 2007 Elsevier Inc. Terms and Conditions

Figure 1 Compartmentalization of Nuclear Processes Transcription, replication, and DNA repair are compartmentalized. (A) Transcription sites visualized by incorporation of bromo-UTP, (B) replication sites visualized by incorporation of bromo-dUTP, and (C) repair sites visualized by accumulation of repair factor 53BP1 at a double-strand break (DSB) are shown. In all cases, components are dynamically recruited from the nucleoplasm as single subunits or small preassembled subcomplexes. (A) is reprinted with permission from Elbi et al., 2002, (B) is courtesy of Rong Wu and David Gilbert at Florida State University, and (C) is courtesy of Evi Soutoglou from the National Cancer Institute, NIH. Cell 2007 128, 787-800DOI: (10.1016/j.cell.2007.01.028) Copyright © 2007 Elsevier Inc. Terms and Conditions

Figure 2 Local Organization of Chromatin Local chromatin loops are essential for (A) transcriptional activation and repression, (B) coordination of initiation and termination/3′ end processing, and (C) boundary function. (D) Giant loops displace gene clusters from the chromosome body. Cell 2007 128, 787-800DOI: (10.1016/j.cell.2007.01.028) Copyright © 2007 Elsevier Inc. Terms and Conditions

Figure 3 Functional Consequences of Global Chromatin Organization (A and B) Spatial clustering of genes on distinct chromosomes facilitates their expression by (A) association with shared transcription and processing sites or (B) physical interactions with regulatory elements on separate chromosomes. (C) The physical proximity of chromosomes contributes to the probability of chromosomal translocations. Cell 2007 128, 787-800DOI: (10.1016/j.cell.2007.01.028) Copyright © 2007 Elsevier Inc. Terms and Conditions

Figure 4 Models of Nuclear Organization (Top left) In a deterministic model a functional site (transcription, for example) is preformed and contains structural elements. In this model, chromosome position is established and maintained by specific interactions of chromosomes with a scaffold. (Top right) In a self-organization model the site forms around a poised gene as a consequence of its activation. In this model, chromosome position is determined by the interaction of functionally equivalent regions on distinct chromosomes. (Bottom) Nuclear architecture is generated by self-organization. Transcription factors are predominantly unbound and diffuse freely though the nucleus in search of specific binding sites. Upon initial transcriptional activation of a particular gene, chromatin is remodeled, and transcription factors are recruited to the gene where they initiate formation of a transcription hub. As pre-mRNA is synthesized, splicing factors are recruited from their storage compartments. At high levels of transcription, multiple genes may coalesce to form a transcription center, which is closely associated with the splicing-factor compartment. The formation of the transcription center does not require the presence of a nuclear scaffold; chromatin is sufficient to serve as an attachment site. The configuration of splicing-factor compartment, transcription factory, and gene locus is generated in a self-organizing manner without the requirement for dedicated structural elements. Cell 2007 128, 787-800DOI: (10.1016/j.cell.2007.01.028) Copyright © 2007 Elsevier Inc. Terms and Conditions