Evolutionary rate heterogeneity of Alu repeats upstream of the APOA5 gene: do they regulate APOA5 expression?

Ruiz-Narváez, Edward A.; Campos, Hannia

doi:10.1007/s10038-008-0245-7

Cited by 7 publications

(3 citation statements)

References 36 publications

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“…Some of these repeats have been reported to contain CTCF binding sites. 67 Unfortunately, it is not clear whether repetitive elements present in the chicken genome are rich in CTCF binding sites.…”

Section: Discussionmentioning

confidence: 99%

The clustering of CpG islands may constitute an important determinant of the 3D organization of interphase chromosomes

Gushchanskaya

Ulyanov

et al. 2014

Epigenetics

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We used the 4C-Seq technique to characterize the genome-wide patterns of spatial contacts of several CpG islands located on chromosome 14 in cultured chicken lymphoid and erythroid cells. We observed a clear tendency for the spatial clustering of CpG islands present on the same and different chromosomes, regardless of the presence or absence of promoters within these CpG islands. Accordingly, we observed preferential spatial contacts between Sp1 binding motifs and other GC-rich genomic elements, including the DNA sequence motifs capable of forming G-quadruplexes. However, an anchor placed in a gene/CpG island-poor area formed spatial contacts with other gene/CpG island-poor areas on chromosome 14 and other chromosomes. These results corroborate the two-compartment model of the spatial organization of interphase chromosomes and suggest that the clustering of CpG islands constitutes an important determinant of the 3D organization of the eukaryotic genome in the cell nucleus. Using the ChIP-Seq technique, we mapped the genome-wide CTCF deposition sites in the chicken lymphoid and erythroid cells that were used for the 4C analysis. We observed a good correlation between the density of CTCF deposition sites and the level of 4C signals for the anchors located in CpG islands but not for an anchor located in a gene desert. It is thus possible that CTCF contributes to the clustering of CpG islands observed in our experiments.

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Section: Discussionmentioning

confidence: 99%

The clustering of CpG islands may constitute an important determinant of the 3D organization of interphase chromosomes

Gushchanskaya

Ulyanov

et al. 2014

Epigenetics

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“…Moreover, a minority of Alu elements display signs of intrinsic functionality including the presence of activating histone modifications and a DNA unmethylated state (Rodriguez et al 2008b;Saito et al 2009;Edwards et al 2010;Yoshida et al 2011;Ward et al 2013;Xie et al 2013;Su et al 2014). The presence of diverse transcription factor binding motifs in Alu sequences is common (Ruiz-Narváez and Campos 2008;Cui et al 2011;Deininger 2011), but motif occupancy appears to be constrained by DNA methylation (Wang et al 2012;Medvedeva et al 2014;Domcke et al 2015;Maurano et al 2015;Schübeler 2015). Hence, hypomethylation of Alu repeats might enable the binding of transcription and epigenetic factors affecting gene activity and genomic architecture in both normal and cancer cells.…”

Section: Individual Features Of Unmethylated Alu Repeats and Functionmentioning

confidence: 99%

The epigenetic landscape of Alu repeats delineates the structural and functional genomic architecture of colon cancer cells

et al. 2016

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Cancer cells exhibit multiple epigenetic changes with prominent local DNA hypermethylation and widespread hypomethylation affecting large chromosomal domains. Epigenome studies often disregard the study of repeat elements owing to technical complexity and their undefined role in genome regulation. We have developed NSUMA (Next-generation Sequencing of UnMethylated Alu), a cost-effective approach allowing the unambiguous interrogation of DNA methylation in more than 130,000 individual Alu elements, the most abundant retrotransposon in the human genome. DNA methylation profiles of Alu repeats have been analyzed in colon cancers and normal tissues using NSUMA and whole-genome bisulfite sequencing. Normal cells show a low proportion of unmethylated Alu (1%-4%) that may increase up to 10-fold in cancer cells. In normal cells, unmethylated Alu elements tend to locate in the vicinity of functionally rich regions and display epigenetic features consistent with a direct impact on genome regulation. In cancer cells, Alu repeats are more resistant to hypomethylation than other retroelements. Genome segmentation based on high/low rates of Alu hypomethylation allows the identification of genomic compartments with differential genetic, epigenetic, and transcriptomic features. Alu hypomethylated regions show low transcriptional activity, late DNA replication, and its extent is associated with higher chromosomal instability. Our analysis demonstrates that Alu retroelements contribute to define the epigenetic landscape of normal and cancer cells and provides a unique resource on the epigenetic dynamics of a principal, but largely unexplored, component of the primate genome.

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“…Interestingly, some Alu elements can function as insulators [121, 123]. Alu elements are capable of transposition, and their relocation within the genome together with CTCF binding sites may cause reorganization of the domain structure, as we proposed earlier for S/MARs-containing retroelements [74].…”

Section: Ctcf and Genome Functioningmentioning

confidence: 95%

Vertebrate Protein CTCF and its Multiple Roles in a Large-Scale Regulation of Genome Activity

Николаев¹,

Akopov²,

Didych³

2009

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The CTCF transcription factor is an 11 zinc fingers multifunctional protein that uses different zinc finger combinations to recognize and bind different sites within DNA. CTCF is thought to participate in various gene regulatory networks including transcription activation and repression, formation of independently functioning chromatin domains and regulation of imprinting. Sequencing of human and other genomes opened up a possibility to ascertain the genomic distribution of CTCF binding sites and to identify CTCF-dependent cis-regulatory elements, including insulators. In the review, we summarized recent data on genomic distribution of CTCF binding sites in the human and other genomes within a framework of the loop domain hypothesis of large-scale regulation of the genome activity. We also tried to formulate possible lines of studies on a variety of CTCF functions which probably depend on its ability to specifically bind DNA, interact with other proteins and form di- and multimers. These three fundamental properties allow CTCF to serve as a transcription factor, an insulator and a constitutive dispersed genome-wide demarcation tool able to recruit various factors that emerge in response to diverse external and internal signals, and thus to exert its signal-specific function(s).

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Evolutionary rate heterogeneity of Alu repeats upstream of the APOA5 gene: do they regulate APOA5 expression?

Cited by 7 publications

References 36 publications

The clustering of CpG islands may constitute an important determinant of the 3D organization of interphase chromosomes

The clustering of CpG islands may constitute an important determinant of the 3D organization of interphase chromosomes

The epigenetic landscape of Alu repeats delineates the structural and functional genomic architecture of colon cancer cells

Vertebrate Protein CTCF and its Multiple Roles in a Large-Scale Regulation of Genome Activity

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