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![(A) ~30 Mb of human chromosome 7 is analyzed at a resolution of 50 Kb; a fine correspondence of isochore boundaries with LAD and TAD boundaries can be observed (modified from [30]). (B) The chromatin loops from a 2.1 Mb region of human chromosome 20 have been aligned with the corresponding heat map which was used to segment the corresponding DNA sequence into isochores; asterisks indicate small anomalies in the isochores/domains correspondence (modified from [30]).](publication/350865244/figure/fig4/AS:1019752537415680@1620139359050/A-30-Mb-of-human-chromosome-7-is-analyzed-at-a-resolution-of-50-Kb-a-fine.png)
(A) ~30 Mb of human chromosome 7 is analyzed at a resolution of 50 Kb; a fine correspondence of isochore boundaries with LAD and TAD boundaries can be observed (modified from [30]). (B) The chromatin loops from a 2.1 Mb region of human chromosome 20 have been aligned with the corresponding heat map which was used to segment the corresponding DNA sequence into isochores; asterisks indicate small anomalies in the isochores/domains correspondence (modified from [30]).
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The chromatin of the human genome was analyzed at three DNA size levels. At the first, compartment level, two “gene spaces” were found many years ago: A GC-rich, gene-rich “genome core” and a GC-poor, gene-poor “genome desert”, the former corresponding to open chromatin centrally located in the interphase nucleus, the latter to closed chromatin loc...
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... lines of evidence indicated the existence of finer correlations of isochores (1) with the "sub-compartments" A1, A2 and B1-B3 based on Hi-C [72] that showed links with gene expression and histone modifications; in this case, A1 sub-compartments were shown to correspond to H2/H3 isochores, A2 sub-compartments to H1 and L2 + isochores, and B1-B3 sub-compartments to L2 -and L1 isochores (see Figure 2B [30]); (2) with LADs and TADs (see Figure 4A), a result obtained for all human and mouse chromosomes [30]; (3) with loop domains (see Figure 4B) [30,83]. [30]). ...
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... lines of evidence indicated the existence of finer correlations of isochores (1) with the "sub-compartments" A1, A2 and B1-B3 based on Hi-C [72] that showed links with gene expression and histone modifications; in this case, A1 sub-compartments were shown to correspond to H2/H3 isochores, A2 sub-compartments to H1 and L2 + isochores, and B1-B3 sub-compartments to L2 -and L1 isochores (see Figure 2B [30]); (2) with LADs and TADs (see Figure 4A), a result obtained for all human and mouse chromosomes [30]; (3) with loop domains (see Figure 4B) [30,83]. [30]). ...
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... is again an important conclusion, if one considers that extrusion was visualized as the only way to explain the formation of the loops [108,111], a view also contradicted by the fact that extrusion may or may not affect "primary TADs". Two important results concern the correspondence of isochores and sub-compartments with LADs and TADs ( Figure 4A) and with loop domains ( Figure 4B). The compositional stability of the GC-poor isochores of LADs across the evolutionary transition between cold-and warm-blooded vertebrates are most likely to be due to their interactions with the lamina as already mentioned. ...
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... is again an important conclusion, if one considers that extrusion was visualized as the only way to explain the formation of the loops [108,111], a view also contradicted by the fact that extrusion may or may not affect "primary TADs". Two important results concern the correspondence of isochores and sub-compartments with LADs and TADs ( Figure 4A) and with loop domains ( Figure 4B). The compositional stability of the GC-poor isochores of LADs across the evolutionary transition between cold-and warm-blooded vertebrates are most likely to be due to their interactions with the lamina as already mentioned. ...
Citations
... Each corresponds to the previously identified gene-dense (compartment A) and gene-poor (compartment B) chromosomal regions, observed by in situ hybridization, occupying the more internal and the more peripheral nuclear compartment, respectively [21,48,49]. TADs organize themselves into autonomous domains of the genome, exerting significant roles in transcriptional regulation, DNA replication, and other processes involving chromatin organization [50,51]. Consequently, the organization of the genome into defined structural domains is a crucial feature for genome functionality, as the previously described in human pigmentation studies related to hair or eye colors [13,[52][53][54][55]. ...
The most significant genetic influence on eye color pigmentation is attributed to the intronic SNP rs12913832 in the HERC2 gene, which interacts with the promoter region of the contiguous OCA2 gene. This interaction, through the formation of a chromatin loop, modulates the transcriptional activity of OCA2, directly affecting eye color pigmentation. Recent advancements in technology have elucidated the precise spatial organization of the genome within the cell nucleus, with chromatin architecture playing a pivotal role in regulating various genome functions. In this study, we investigated the organization of the chromatin close to the HERC2/OCA2 locus in human lymphocyte nuclei using fluorescence in situ hybridization (FISH) and high-throughput chromosome conformation capture (Hi-C) data. The 3 Mb of genomic DNA that belonged to the chromosomal region 15q12-q13.1 revealed the presence of three contiguous chromatin loops, which exhibited a different level of compaction depending on the presence of the A or G allele in the SNP rs12913832. Moreover, the analysis of the genomic organization of the genes has demonstrated that this chromosomal region is evolutionarily highly conserved, as evidenced by the analysis of syntenic regions in species from other Vertebrate classes. Thus, the role of rs12913832 variant is relevant not only in determining the transcriptional activation of the OCA2 gene but also in the chromatin compaction of a larger region, underscoring the critical role of chromatin organization in the proper regulation of the involved genes. It is crucial to consider the broader implications of this finding, especially regarding the potential regulatory role of similar polymorphisms located within intronic regions, which do not influence the same gene by modulating the splicing process, but they regulate the expression of adjacent genes. Therefore, caution should be exercised when utilizing whole-exome sequencing for diagnostic purposes, as intron sequences may provide valuable gene regulation information on the region where they reside. Thus, future research efforts should also be directed towards gaining a deeper understanding of the precise mechanisms underlying the role and mode of action of intronic SNPs in chromatin loop organization and transcriptional regulation.
... In vertebrates, the genome was shown to be organized into two major components with specific functionalities [82] according to guanine plus cytosine (GC) content. The base changes during vertebrate evolution were such that the GC-poor compartment remained poor in cold-blooded vertebrates (fishes, amphibians, reptiles), but their GC-rich compartment became even richer in GC during their transition to warm-blooded vertebrates (mammals and birds). ...
... The base changes during vertebrate evolution were such that the GC-poor compartment remained poor in cold-blooded vertebrates (fishes, amphibians, reptiles), but their GC-rich compartment became even richer in GC during their transition to warm-blooded vertebrates (mammals and birds). This compositional transition led to a range of functional adaptations at the molecular level [82]. The effect of this major transition [83] on the genome structure of modern species of both groups can still be observed through GC composition at the regional level, which led Bernardi to coin the term isochores in 2007 for DNA stretches larger than 300 Kbp that do not vary by more than an average standard deviation of~2% GC [84]. ...
Environmental stresses, such as drought, have negative effects on crop yield. Drought is a stress whose impact tends to increase in some critical regions. However, the worldwide population is continuously increasing and climate change may affect its food supply in the upcoming years. Therefore, there is an ongoing effort to understand the molecular processes that may contribute to improving drought tolerance of strategic crops. These investigations should contribute to delivering drought-tolerant cultivars by selective breeding. For this reason, it is worthwhile to review regularly the literature concerning the molecular mechanisms and technologies that could facilitate gene pyramiding for drought tolerance. This review summarizes achievements obtained using QTL mapping, genomics, synteny, epigenetics, and transgenics for the selective breeding of drought-tolerant wheat cultivars. Synthetic apomixis combined with the msh1 mutation opens the way to induce and stabilize epigenomes in crops, which offers the potential of accelerating selective breeding for drought tolerance in arid and semi-arid regions.
... A classic example is the presence of isochores that separate by Giemsa staining and by density centrifugation. In mammals, GC-rich isochores are considered to replicate earlier in the cell cycle than AT-rich isochores, and also have a greater density of genes which are more compact (Bernardi, 2021;Constantini and Musto 2017). Analyses of the chicken B locus illustrate regions that differ in another way: the BF-BL region (which corresponds to the major histocompatibility complex, MHC) is relatively compact and stable with little obvious recombination, whereas the BG region undergoes frequent expansion and contraction leading to copy number variation (CNV). ...
The chicken continues to hold its position as a leading model organism within many areas of research, as well as a being major source of protein for human consumption. The First Report on Chicken Genes and Chromosomes [Schmid et al., 2000], which was published in 2000, was the brainchild of the late, and sadly missed, Prof Michael Schmid of the University of Würzburg. It was a publication bringing together updates on the latest research and resources in chicken genomics and cytogenetics. The success of this First report led to the subsequent publication of the Second [Schmid et al., 2005] and Third [Schmid et al., 2015] reports proving popular references for the research community. It is now our pleasure to be able to introduce publication of the Fourth report. Being seven years since the last report, this publication captures the many advances that have taken place during that time. This includes presentation of the detailed genomic resources that are now available, largely due to increasing capabilities of sequencing technologies and which herald the pangenomic age, allowing for a much richer and more complete knowledge of the avian genome. Ongoing cytogenetic work also allows for examination of chromosomes, specific elements within chromosomes and the evolutionary history and comparison of karyotypes. We also examine chicken research efforts with a much more ‘global’ outlook with a greater impact on food security and the impact of climate change, and highlight the efforts of international consortia, such as the Chicken Diversity Consortium. We dedicate this Report to Michael.
... Several research groups have shown that a large part of what previously was considered "junk" DNA is actually transcribed [36] and at least part of it has important cellular functions [37,38]. Among the important transcribed DNA regions, non-coding RNAs genes have proven to be an enormous source of previously unknown regulatory elements that take part in physiological and pathological states. ...
... Since the discovery that most of the human DNA is transcribed and have a potential function [36][37][38], extensive research has shown that non-coding RNAs genes provide a large number of regulatory elements in cancer. Due to the sheer number of these molecules and lower evolutionary conservation compared to coding DNA, we have only a fragmentary glimpse of their function in these diseases. ...
Breast cancer is the leading cause of cancer-related deaths in women worldwide. In the United States, even with earlier diagnosis and treatment improvements, the decline in mortality has stagnated in recent years. More research is needed to provide better diagnostic, prognostic, and therapeutic tools for these patients. Long non-coding RNAs are newly described molecules that have extensive roles in breast cancer. Emerging reports have shown that there is a strong link between these RNAs and the hypoxic response of breast cancer cells, which may be an important factor for enhanced tumoral progression. In this review, we summarize the role of hypoxia-associated lncRNAs in the classic cancer hallmarks, describing their effects on the upstream and downstream hypoxia signaling pathway and the use of them as diagnostic and prognostic tools.
... For a long time, non-coding DNA sequences was called as "junk DNA". It is mainly represented by repeated sequences (or repeats) of different sizes scattered between (or within) the genes, for which, recent studies are increasingly demonstrating its interest and function in the genome (Bernardi, 2021). A repetitive sequence can be considered as a substring that can be found in several occurrences in the main string on the alphabet {A, C, G, T}. ...
Genomic variation is induced by numerous factors simultaneously, which results in a set of genomic behaviours related to its structure, architecture, expression, evolution, etc, which could be referred to as genome dynamics. During my thesis project, we chose to focus on three major players impacting genome dynamics:- Chromatin structure: unevenly compacted along chromosomes;- Meiotic recombination landscape: reflecting the frequency variations of exchanging DNA fragments during cell division;- Repetitive DNA: mainly Transposable Elements (TEs) inducing genome assembly errors.Firstly, We propose an automated computational tool, based on the Marey maps method, allowing to identify heterochromatin boundaries along chromosomes and estimating local recombination rates. Our method, called BREC (heterochromatin Boundaries and RECombination rate estimates) is non-genome-specific, running even on non-model genomes as long as genetic and physical maps are available. BREC is a statistic-based data-driven tool. Therefore, a data pre-processing module (data quality control and cleaning) is provided. BREC results would allow conducting more broadly an analysis with a comparative genomics approach on their identified heterochromatin regions in terms of recombination landscape, TE density, etc.Secondly, in order to address the genome assembly process which is strongly impacted by the TE abundance, one type of repeats, we chose to focus on the scaffolding step with the aim of enhancing the assembly quality by exploiting the analysis of repeated regions and proposing a pipeline of improvement.Thirdly, with the aim of testing the veracity of the approaches and tools developed but also to return to the analysis of mosquito genomes, we present a case study combining the application results on the variations in recombination rate along these genomes, as well as and the organization of chromatin domains, with respect to the TE distribution along each chromosome. The preliminary findings suggest a correlation between the distribution of certain TE families and the chromatin domains.To conclude this thesis manuscript, we present an opening concerning genomes dynamics with respect to the different aspects addressed. Then, we present the conceptual, application, and technical limits identified by our experimental design. Finally, we suggest a few perspectives on the scope of our contributions beyond my PhD project.
... Condensed chromatin or heterochromatin is formed by 30 nm fibers or greater degree of packing with tight contacts between nucleosomes; it is rich in AT bases and poor in GC bases [20]. Heterochromatin mainly contains non-coding DNA sequences, especially repetitive sequences such as α, β, γ, I, II, and II satellite sequences; micro-, mini-, and macro-satellites; and diverse transposon types [13]. ...
Cellular identity is determined through complex patterns of gene expression. Chromatin, the dynamic structure containing genetic information, is regulated through epigenetic modulators, mainly by the histone code. One of the main challenges for the cell is maintaining functionality and identity, despite the accumulation of DNA damage throughout the aging process. Replicative cells can remain in a senescent state or develop a malign cancer phenotype. In contrast, post-mitotic cells such as pyramidal neurons maintain extraordinary functionality despite advanced age, but they lose their identity. This review focuses on tau, a protein that protects DNA, organizes chromatin, and plays a crucial role in genomic stability. In contrast, tau cytosolic aggregates are considered hallmarks of Alzheimer´s disease (AD) and other neurodegenerative disorders called tauopathies. Here, we explain AD as a phenomenon of chromatin dysregulation directly involving the epigenetic histone code and a progressive destabilization of the tau–chromatin interaction, leading to the consequent dysregulation of gene expression. Although this destabilization could be lethal for post-mitotic neurons, tau protein mediates profound cellular transformations that allow for their temporal survival.
... Condensed chromatin or heterochromatin is formed by 30 nm fibers or greater degree of packing with tight contacts between nucleosomes; it is rich in AT bases and poor in GC bases [20]. Heterochromatin mainly contains non-coding DNA sequences, especially repetitive sequences such as α, β, γ, I, II, and II satellite sequences; micro-, mini-, and macro-satellites; and diverse transposon types [13]. ...
Tandem repeats can play an important role in centromere structure, subtelomeric regions, DNA methylation, recombination, and the regulation of gene activity. There is a growing need for bioinformatics tools that can visualize and explore chromosome-scale repeats. Here we present RepeatOBserver, a new tool for visualizing tandem repeats and clustered transposable elements and for identifying potential natural centromere locations, using a Fourier transform of DNA walks: https://github.com/celphin/RepeatOBserverV1. RepeatOBserver can identify a broad range of repeats (3-20,000bp long) in genome assemblies without any a priori knowledge of repeat sequences or the need for optimizing parameters. RepeatOBserver allows for easy visualization of the positions of both perfect and imperfect repeating sequences across each chromosome. We use RepeatOBserver to compare DNA walks, repeat patterns and centromere positions across genome assemblies in a wide range of well-studied species (e.g., human, mouse-ear cress), crops, and non-model organisms (e.g., fern, yew). Analyzing 107 chromosomes with known centromere positions, we find that centromeres consistently occur in regions that have the least diversity in repeat types (i.e. one or a few repeated sequences are present in very high numbers). Taking advantage of this information, we use a genomic Shannon diversity index to predict centromere locations in several other chromosome-scale genome assemblies. The Fourier spectra produced by RepeatOBserver can help visualize historic centromere positions, potential neocentromeres, retrotransposon clusters and gene copy variation. Identification of patterns of split and inverted tandem repeats at inversion boundaries suggests that at least some chromosomal inversions can be predicted with RepeatOBserver. RepeatOBserver is therefore a flexible tool for comprehensive characterization of tandem repeat patterns that can be used to visualize and identify a variety of regions of interest in genome assemblies.
Hypoxia is one of the hallmarks of solid tumors, especially in hepatocellular carcinoma (HCC). CircRNAs are reported to be tightly connected to hypoxia and also have essential roles in cancer progression. However, many circRNAs implicated in hypoxia-mediated HCC progression are still unclear and require further exploration. In this study, a hypoxia cell model was structured by exposing cells to hypoxia conditions (1% O2) and normoxia conditions (21% O2) as a control. The effects of hypoxia and normoxia on cell viability, migration, invasion, and glycolysis were examined. The expressions of circRNARTN4IP1 under hypoxia were identified. Finally, molecular mechanisms and biological function of circRTN4IP1 were explored. We confirmed that hypoxia treatment facilitated capacities of proliferation, migration, invasion, and glycolysis in tumor cells. Hypoxia induced a significant increase expression of circRTN4IP1 in cells. Functionally, knockdown of circRTN4IP1 inhibited cell malignant progression and glycolysis under hypoxia HCC cells. Mechanistically, HIF1A targeted the promoter region of circRTN4IP1 and positively regulated the expression of circRTN4IP1. In addition, circRTN4IP1 targeted miR-532-5p/G6PC3 axis. In short, hypoxia induced activation of the HIF1A/circRTN4IP1/miR-532-5p/G6PC3 signaling axis, which promoted proliferation, migration, invasion, and glycolysis of HCC cells. This study may reveal a possible mechanism driving the progression of hypoxia HCC, so as to find potential effective candidates for targeting hypoxia microenvironment therapy.
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