Isochores & interphase chromatin^(a).

<p>^(a)HK, housekeeping; TSS, transcription start sites.</p><p>^(b)<i>Drosophila</i>. Other data concern mammalian cells.</p><p>^(c)see also Text.</p><p>Isochores & interphase chromatin<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0143739#t002fn001" target="_blank">^(a)</a>.</p

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.

<p>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.</p

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 compa

<p>A. Compositional profile of human chromosome 21 (from the hg19 release) as seen through non-overlapping 100-Kb windows, using the IsoSegmenter program [<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0143739#pone.0143739.ref015" target="_blank">15</a>]. 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 <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0143739#pone.0143739.s001" target="_blank">S1 Table</a>). 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. [<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0143739#pone.0143739.ref016" target="_blank">16</a>]). 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 <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0143739#pone.0143739.t001" target="_blank">Table 1</a>) 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.</p

Chromosome architecture changes through the cell cycle.

<p>The changes in chromosome architecture from interphase to mitosis are reversible.</p><p>Chromosome architecture changes through the cell cycle.</p

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.

<p>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.</p

GC levels of prometaphase (A) and metaphase (B) bands of chromosome 1.

<p>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.</p

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.

<p>Vertical red lines indicate the borders of isochore families.</p

Chromatin loops and isochores from a 2.1 Mb region of human chromosome 20.

<p>The chromatin loops from a 2.1 Mb region of human chromosome 20 (Fig 6F from [<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0168023#pone.0168023.ref003" target="_blank">3</a>]) have been aligned with the corresponding heat map which was used to segment the corresponding DNA sequence into isochores. In this Figure the “extended” isochore ranges of Table A in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0168023#pone.0168023.s001" target="_blank">S1 File</a> were used to assign isochores to families, in order to take care of some minimal trespassings of the 46% GC upper threshold of H1 isochores. Asterisks indicate anomalies in the isochores/domains correspondence (see Text).</p

An Isochore Framework Underlies Chromatin Architecture

<div><p>A recent investigation showed the existence of correlations between the architectural features of mammalian interphase chromosomes and the compositional properties of isochores. This result prompted us to compare maps of the Topologically Associating Domains (TADs) and of the Lamina Associated Domains (LADs) with the corresponding isochore maps of mouse and human chromosomes. This approach revealed that: 1) TADs and LADs correspond to isochores, <i>i</i>.<i>e</i>., isochores are the genomic units that underlie chromatin domains; 2) the conservation of TADs and LADs in mammalian genomes is explained by the evolutionary conservation of isochores; 3) chromatin domains corresponding to GC-poor isochores (<i>e</i>.<i>g</i>., LADs) show not only self-interactions but also intrachromosomal interactions with other domains also corresponding to GC-poor isochores even if located far away; in contrast, chromatin domains corresponding to GC-rich isochores (<i>e</i>.<i>g</i>., TADs) show more localized chromosomal interactions, many of which are inter-chromosomal. In conclusion, this investigation establishes a link between DNA sequences and chromatin architecture, explains the evolutionary conservation of TADs and LADs and provides new information on the spatial distribution of GC-poor/gene-poor and GC-rich/gene-rich chromosomal regions in the interphase nucleus.</p></div

Inter-chromosomal interactions and isochores.

<p>The heat maps of chromatin interactions of human chromosomes 7 and 10 (from [<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0168023#pone.0168023.ref003" target="_blank">3</a>]) are compared with the corresponding compositional and LAD profiles (from [<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0168023#pone.0168023.ref007" target="_blank">7</a>]). Interactions appear to correspond to GC-rich isochores and inter-LADS and to be widely spread over the two chromosomes. Lines are used to guide the visual inspection of these features.</p