Fig 1.
A. Compositional profile of human chromosome 21 (from the hg19 release) as seen through non-overlapping 100-Kb windows, using the IsoSegmenter program [15]. DNA stretches from isochore families L1 to H3 are represented here in different colors, deep blue, light blue, yellow, orange, red, respectively. The ordinate values are the minima GC values (valleys) between isochore families (see S1 Table). The red horizontal line at 41% GC separates the two (GC-poor and GC-rich) genome compartments. B. Isochore families. The histogram displays the isochores from the human genome as pooled in bins of 1% GC (modified from ref. [16]). The Gaussian profile shows the distribution of isochore families, which are represented in different colors as in Fig 1A. Gene densities (and all other structural and functional properties tested; see Table 1) define a genome desert, isochore families L1, L2, H1, and a genome core, isochore families H2, H3 (separated by a vertical broken red line). C. The scheme compares isochores belonging to the genome desert and to the genome core with chromatin domains and chromatin boundaries.
Table 1.
Structural and functional properties of the genome core vs. the genome desert (a).
Fig 2.
A. A scheme of an interphase chromatin loop (a topologically associating domain, TAD, with three sub-domains in this figure). The DNA framework of the loop is a large GC-poor isochore. The loop is closed by anchors (chromatin boundaries) that interact with two architectural proteins, CTCF (boxes) and cohesin (green oval). A number of sub-domains have their loops anchored by CTCF and cohesin sub-units (boxes) (see Text). B. Opening of the three-dimensional architecture of the domains and sub-domains in a linear chromatin structure, possibly in a “beads-on-a string”, 10-nm conformation. Architectural proteins are visualized as still linked to their binding sites (see Text). C, D. Folding of the open structure into 30-nm fiber loops anchored by the architectural proteins and compaction into three early prophase, single-isochore bands R-G-R, the central one being a multiple-loop band, the flanking ones single-loop bands. E. Coalescence of single-isochore bands into multiple-isochore bands. In the example shown, the R-G-R single-isochore bands coalesce into an R band because of a “majority rule” (2 R vs. 1 G). Architectural proteins form a discontinuous protein scaffold of the chromosome (see Text).
Table 2.
Isochores & interphase chromatin(a).
Fig 3.
The percentages of single-isochore bands are plotted against the total number of bands at metaphase (400 bands), prometaphase (850 bands) and mid-prophase (1,700 bands) and extrapolated to 100% single-isochore bands.
Fig 4.
The banding pattern of chromosome 21: (A), at early prophase, (B), at prometaphase and (C) at metaphase. Vertical lines connect early prophase bands formed by single isochores (marked by red asterisks) or isochore blocks (the macroisochores) with prometaphase bands. B→C. The following coalescence process leads to different ratios of prometaphase to metaphase bands, 1:1, 3:1, 5:1. A’ B’ C’. The compositional profiles A’ of isochores (early prophase); B’ macroisochores (prometaphase) and C’ megaisochores (metaphase). D, E. GC levels of prometaphase (D) and metaphase (E) bands.
Blue and red points indicate G and R bands. Red arrows and asterisks indicate single-isochore bands. The red horizontal line separates the two genome compartments, GC-poor and GC-rich.
Fig 5.
GC levels of prometaphase (A) and metaphase (B) bands of chromosome 1.
Black arrows indicate p/q arms intervals, blue and red points indicates G and R bands, arrows single-isochore bands. Horizontal broken lines indicate the GC boundaries of isochore families. C. Scheme of the coalescence of prometaphase into metaphase bands.
Fig 6.
Amounts of 2-Kb sequences <35% GC as present in 50-Kb stretches of chromosome 21 are plotted against the GC levels of the 50-Kb stretches.
Vertical red lines indicate the borders of isochore families.
Table 3.
Chromosome architecture changes through the cell cycle.
Fig 7.
Isochores, chromosomal bands and chromosome architecture.
Interphase: See legends of Figs 1C and 2, for the top and bottom panels respectively. Prophase: See legend of Fig 2. The R band of prophase coalesces with two flanking G bands producing a G band. Prometaphase to Metaphase: The multiple-isochore prometaphase bands coalesce further into metaphase bands (see legend of Fig 5C). The central R band of prophase coalesces with two G bands giving rise to a larger G band. The 30-nm loops have different sizes and orientations (the figure is from ref. [64]); the protein scaffold is discontinuous (see Text).