Genome Architecture: Domain Organization of Interphase Chromosomes Wendy A. Bickmore, Bas van Steensel  Cell  Volume 152, Issue 6, Pages 1270-1284 (March 2013) DOI: 10.1016/j.cell.2013.02.001 Copyright © 2013 Elsevier Inc. Terms and Conditions

Figure 1 Chromatin Types (A) Size distribution (in base pairs) of some genome features (blue) and various types of chromatin domains in human fibroblasts (red). Numbers on the righthand side indicate approximate genome-wide counts of the respective domains. Note that the sizes and counts of chromatin domains can vary between cell types and can depend much on the algorithm used to define the domains. (Data are from http://genome.ucsc.edu; Costantini et al., 2006; Guelen et al., 2008; Lister et al., 2009; Hawkins et al., 2010; Dixon et al., 2012; Pope et al., 2012.) (B) Cartoon model of a chromosomal fiber, illustrating its segmentation into domains of distinct chromatin types, each consisting of a specific combination of proteins and histone modifications (indicated by colors). (C) Classification of chromatin types. This example shows binding maps of 12 chromatin proteins along a part of chromosome 2L in Drosophila Kc cells. Computer algorithms are used to search for recurrent combinations of proteins (chromatin “types” or “states”) and to subsequently define linear chromosomal domains covered by these types (highlighted in different colors; the classification in this example was based on 53 protein profiles). Note that some proteins are present in a single chromatin type, whereas others can be shared among multiple types. Adapted from Filion and van Steensel (2010). Cell 2013 152, 1270-1284DOI: (10.1016/j.cell.2013.02.001) Copyright © 2013 Elsevier Inc. Terms and Conditions

Figure 2 Radial Organization in the Nucleus, within and between Chromosomes (A) mESC nucleus hybridized by FISH with a paint for mouse chromosome 2 (green) and a probe (red) for just the exome of mouse chromosome 2 (Boyle et al., 2011). This demonstrates the looping-out of the gene-dense regions from the core chromosome territory and their disposition away from the nuclear periphery and toward the interior of the nucleus. (B) Human lymphoblastoid cell nucleus hybridized by FISH with paint for the gene-rich human chromosome 19 (red) and gene-poor chromosome 18 (green) reveals the radial organization of chromosomes in the nucleus. (C) Courtesy of Frank Alber (University of Southern California). A density contour plot for the localization probability (red = max, green = min) of human chromosomes 1, 11, 14, 15, 16, 17, 19, 20, 21, and 22 in lymphoblastoid cell nuclei modeled from Hi-C data recapitulates the clustering of gene-rich chromosomes in the center of the nucleus, along with the rDNA-containing acrocentric chromosomes (Kalhor et al., 2012). Cell 2013 152, 1270-1284DOI: (10.1016/j.cell.2013.02.001) Copyright © 2013 Elsevier Inc. Terms and Conditions

Figure 3 Long-Range Interactions among Polycomb Domains in Drosophila (A) Interaction profile of the Polycomb target gene Ant-B (position indicated by red triangle) as determined by 4C. Data are shown as a domainogram, which visualizes the statistical significance (purple: moderately significant; red: highly significant) of the detected interactions for each chromosomal position. Vertical axis represents the resolution at which the significance was calculated (see Tolhuis et al., 2011 for details). Note that the interactions mostly overlap with Polycomb domains (blue boxes) yet are restricted to one chromosome arm. (B) Effect of a chromosomal inversion that joins the two red segments and the two blue segments. Data are plotted in the same order as in (A) for easy comparison. Note that Ant-B now interacts with several loci that were previously on the other chromosome arm and no longer with loci that are moved toward the other arm. (C) Cartoon interpretation of (A), illustrating the stochastic contacts of Ant-B (red triangle) with various Polycomb domains on the same chromosome arm. Cell 2013 152, 1270-1284DOI: (10.1016/j.cell.2013.02.001) Copyright © 2013 Elsevier Inc. Terms and Conditions

Figure 4 Topologically Associating Domains (A) Matrix plot showing all pairwise interaction frequencies captured by 5C (color scale white—blue—black) among loci in an ∼4.5 Mb region on the X chromosome in mESCs. TADs are the large, discrete blocks within which the pairwise contacts are relatively frequent. Gray area corresponds to a repetitive region that could not be probed. (B) H3K27me3 distribution (Marks et al., 2009) and Lamin B1 interactions (Peric-Hupkes et al., 2010) in the same region. Note the partial overlap with TADs. Images in (A) and (B) are courtesy of Elphège Nora (Institut Curie). Cell 2013 152, 1270-1284DOI: (10.1016/j.cell.2013.02.001) Copyright © 2013 Elsevier Inc. Terms and Conditions