No Isochores in the Human Chromosomes 21 and 22?

Häring, David; Kypr, Jaroslav

doi:10.1006/bbrc.2000.4162

Cited by 31 publications

(8 citation statements)

References 21 publications

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“…Isochore membership, therefore, failed to distinguish the two types of genes. Several recent studies have concluded that isochores, while excellent for broad descriptions of chromosomal properties, lack the resolution necessary to analyze subtle influences on gene expression (Häring and Kypr, 2001;Lander et al, 2001;Cohen et al, 2005). Alu enrichment was only 16% correlated with housekeeping genes, but even this modest correlation was highly significant.…”

Section: Housekeeping Genes Are Distinguished By a Distinct Repetitivmentioning

confidence: 99%

Repetitive sequence environment distinguishes housekeeping genes

Eller¹,

Regelson²,

Merriman³

et al. 2007

Gene

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Housekeeping genes are expressed across a wide variety of tissues. Since repetitive sequences have been reported to influence the expression of individual genes, we employed a novel approach to determine whether housekeeping genes can be distinguished from tissue-specific genes their repetitive sequence context. We show that Alu elements are more highly concentrated around housekeeping genes while various longer (>400-bp) repetitive sequences ("repeats"), including Long Interspersed Nuclear Element 1 (LINE-1) elements, are excluded from these regions. We further show that isochore membership does not distinguish housekeeping genes from tissue-specific genes and that repetitive sequence environment distinguishes housekeeping genes from tissue-specific genes in every isochore. The distinct repetitive sequence environment, in combination with other previously published sequence properties of housekeeping genes, were used to develop a method of predicting housekeeping genes on the basis of DNA sequence alone. Using expression across tissue types as a measure of success, we demonstrate that repetitive sequence environment is by far the most important sequence feature identified to date for distinguishing housekeeping genes.

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Section: Housekeeping Genes Are Distinguished By a Distinct Repetitivmentioning

confidence: 99%

Repetitive sequence environment distinguishes housekeeping genes

Eller¹,

Regelson²,

Merriman³

et al. 2007

Gene

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show abstract

“…Some misunderstandings about isochores ( Häring and Kypr 2001 ; Lander et al 2001 ; Belle e al. 2002; Ream et al 2003 ; Cohen et al 2005 ; Elhaik et al 2009 ) were promptly corrected ( Bernardi 2001 ; Clay and Bernardi 2001 , 2002 , 2005 , 2011 ; Clay et al 2003 ; Jabbari et al 2003 ).…”

Section: Introductionmentioning

confidence: 99%

TheAnolisLizard Genome: An Amniote Genome without Isochores?

et al. 2016

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Two articles published 5 years ago concluded that the genome of the lizard Anolis carolinensis is an amniote genome without isochores. This claim was apparently contradicting previous results on the general presence of an isochore organization in all vertebrate genomes tested (including Anolis). In this investigation, we demonstrate that the Anolis genome is indeed heterogeneous in base composition, since its macrochromosomes comprise isochores mainly from the L2 and H1 families (a moderately GC-poor and a moderately GC-rich family, respectively), and since the majority of the sequenced microchromosomes consists of H1 isochores. These families are associated with different features of genome structure, including gene density and compositional correlations (e.g., GC3 vs flanking sequence GC and intron GC), as in the case of mammalian and avian genomes. Moreover, the assembled Anolis chromosomes have an enormous number of gaps, which could be due to sequencing problems in GC-rich regions of the genome. In conclusion, the Anolis genome is no exception to the general rule of an isochore organization in the genomes of vertebrates (and other eukaryotes).

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“…These segments were first defined as having a size greater than 300 kbp. However, many controversies have emerged about the difficulty of identifying such segments in the genome [ 22 , 23 , 24 ]. This controversy led to a more flexible definition of the isochores, with respect to segment size [ 25 , 26 ].…”

Section: Introductionmentioning

confidence: 99%

Nanodosimetric Calculations of Radiation-Induced DNA Damage in a New Nucleus Geometrical Model Based on the Isochore Theory

Thibaut

Tang

Tran

et al. 2022

IJMS

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Double-strand breaks (DSBs) in nuclear DNA represents radiation-induced damage that has been identified as particularly deleterious. Calculating this damage using Monte Carlo track structure modeling could be a suitable indicator to better assess and anticipate the side-effects of radiation therapy. However, as already demonstrated in previous work, the geometrical description of the nucleus and the DNA content used in the simulation significantly influence damage calculations. Therefore, in order to obtain accurate results, this geometry must be as realistic as possible. In this study, a new geometrical model of an endothelial cell nucleus and DNA distribution according to the isochore theory are presented and used in a Monte Carlo simulation chain based on the Geant4-DNA toolkit. In this theory, heterochromatin and euchromatin compaction are distributed along the genome according to five different families (L1, L2, H1, H2, and H3). Each of these families is associated with a different hetero/euchromatin rate related to its compaction level. In order to compare the results with those obtained using a previous nuclear geometry, simulations were performed for protons with linear energy transfers (LETs) of 4.29 keV/µm, 19.51 keV/µm, and 43.25 keV/µm. The organization of the chromatin fibers at different compaction levels linked to isochore families increased the DSB yield by 6–10%, and it allowed the most affected part of the genome to be identified. These new results indicate that the genome core is more radiosensitive than the genome desert, with a 3–8% increase in damage depending on the LET. This work highlights the importance of using realistic distributions of chromatin compaction levels to calculate radio-induced damage using Monte Carlo simulation methods.

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No Isochores in the Human Chromosomes 21 and 22?

Cited by 31 publications

References 21 publications

Repetitive sequence environment distinguishes housekeeping genes

Repetitive sequence environment distinguishes housekeeping genes

TheAnolisLizard Genome: An Amniote Genome without Isochores?

Nanodosimetric Calculations of Radiation-Induced DNA Damage in a New Nucleus Geometrical Model Based on the Isochore Theory

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