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Chromosome Architecture and Genome Organization.

Bernardi G - PLoS ONE (2015)

Bottom Line: This is a critical range that encompasses isochores, interphase chromatin domains and boundaries, and chromosomal bands.The solution rests on the following key points: 1) the transition from the looped domains and sub-domains of interphase chromatin to the 30-nm fiber loops of early prophase chromosomes goes through the unfolding into an extended chromatin structure (probably a 10-nm "beads-on-a-string" structure); 2) the architectural proteins of interphase chromatin, such as CTCF and cohesin sub-units, are retained in mitosis and are part of the discontinuous protein scaffold of mitotic chromosomes; 3) the conservation of the link between architectural proteins and their binding sites on DNA through the cell cycle explains the "mitotic memory" of interphase architecture and the reversibility of the interphase to mitosis process.The results presented here also lead to a general conclusion which concerns the existence of correlations between the isochore organization of the genome and the architecture of chromosomes from interphase to metaphase.

View Article: PubMed Central - PubMed

Affiliation: Science Department, Roma Tre University, Marconi, Rome, Italy.

ABSTRACT
How the same DNA sequences can function in the three-dimensional architecture of interphase nucleus, fold in the very compact structure of metaphase chromosomes and go precisely back to the original interphase architecture in the following cell cycle remains an unresolved question to this day. The strategy used to address this issue was to analyze the correlations between chromosome architecture and the compositional patterns of DNA sequences spanning a size range from a few hundreds to a few thousands Kilobases. This is a critical range that encompasses isochores, interphase chromatin domains and boundaries, and chromosomal bands. The solution rests on the following key points: 1) the transition from the looped domains and sub-domains of interphase chromatin to the 30-nm fiber loops of early prophase chromosomes goes through the unfolding into an extended chromatin structure (probably a 10-nm "beads-on-a-string" structure); 2) the architectural proteins of interphase chromatin, such as CTCF and cohesin sub-units, are retained in mitosis and are part of the discontinuous protein scaffold of mitotic chromosomes; 3) the conservation of the link between architectural proteins and their binding sites on DNA through the cell cycle explains the "mitotic memory" of interphase architecture and the reversibility of the interphase to mitosis process. The results presented here also lead to a general conclusion which concerns the existence of correlations between the isochore organization of the genome and the architecture of chromosomes from interphase to metaphase.

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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).
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pone.0143739.g002: 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).

Mentions: The architecture of interphase chromatin may be schematically visualized, at least for the purpose of the present work, as a set of looped domains and boundaries (see Fig 1C). While domain boundaries generally correspond to (short) GC-rich isochores anchored by architectural proteins, such as CTCF and cohesin (present as a ring structure or as cohesin sub-units), looped domains correspond to (long) GC-poor isochores. In turn, looped domains essentially consist of sub-domains, most of which are anchored by CTCF and by cohesin sub-units (as shown in Fig 2A).


Chromosome Architecture and Genome Organization.

Bernardi G - PLoS ONE (2015)

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).
© Copyright Policy
Related In: Results  -  Collection

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Show All Figures
getmorefigures.php?uid=PMC4664426&req=5

pone.0143739.g002: 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).
Mentions: The architecture of interphase chromatin may be schematically visualized, at least for the purpose of the present work, as a set of looped domains and boundaries (see Fig 1C). While domain boundaries generally correspond to (short) GC-rich isochores anchored by architectural proteins, such as CTCF and cohesin (present as a ring structure or as cohesin sub-units), looped domains correspond to (long) GC-poor isochores. In turn, looped domains essentially consist of sub-domains, most of which are anchored by CTCF and by cohesin sub-units (as shown in Fig 2A).

Bottom Line: This is a critical range that encompasses isochores, interphase chromatin domains and boundaries, and chromosomal bands.The solution rests on the following key points: 1) the transition from the looped domains and sub-domains of interphase chromatin to the 30-nm fiber loops of early prophase chromosomes goes through the unfolding into an extended chromatin structure (probably a 10-nm "beads-on-a-string" structure); 2) the architectural proteins of interphase chromatin, such as CTCF and cohesin sub-units, are retained in mitosis and are part of the discontinuous protein scaffold of mitotic chromosomes; 3) the conservation of the link between architectural proteins and their binding sites on DNA through the cell cycle explains the "mitotic memory" of interphase architecture and the reversibility of the interphase to mitosis process.The results presented here also lead to a general conclusion which concerns the existence of correlations between the isochore organization of the genome and the architecture of chromosomes from interphase to metaphase.

View Article: PubMed Central - PubMed

Affiliation: Science Department, Roma Tre University, Marconi, Rome, Italy.

ABSTRACT
How the same DNA sequences can function in the three-dimensional architecture of interphase nucleus, fold in the very compact structure of metaphase chromosomes and go precisely back to the original interphase architecture in the following cell cycle remains an unresolved question to this day. The strategy used to address this issue was to analyze the correlations between chromosome architecture and the compositional patterns of DNA sequences spanning a size range from a few hundreds to a few thousands Kilobases. This is a critical range that encompasses isochores, interphase chromatin domains and boundaries, and chromosomal bands. The solution rests on the following key points: 1) the transition from the looped domains and sub-domains of interphase chromatin to the 30-nm fiber loops of early prophase chromosomes goes through the unfolding into an extended chromatin structure (probably a 10-nm "beads-on-a-string" structure); 2) the architectural proteins of interphase chromatin, such as CTCF and cohesin sub-units, are retained in mitosis and are part of the discontinuous protein scaffold of mitotic chromosomes; 3) the conservation of the link between architectural proteins and their binding sites on DNA through the cell cycle explains the "mitotic memory" of interphase architecture and the reversibility of the interphase to mitosis process. The results presented here also lead to a general conclusion which concerns the existence of correlations between the isochore organization of the genome and the architecture of chromosomes from interphase to metaphase.

Show MeSH