Mapping long-range chromatin organization within the chicken α-globin gene domain using oligonucleotide DNA arrays

Ioudinkova, E. S.; Petrov, Andrei; Razin, Sergey V.; Vassetzky, Yegor S.

doi:10.1016/j.ygeno.2004.09.008

Cited by 22 publications

(29 citation statements)

References 40 publications

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“…It thus appeared important to explore whether this property was conserved for FR/ MARs present in the constructs used here to generate stable transfectants. To this purpose, we used the in vivo nuclear matrix mapping assay we have previously described (Ioudinkova et al 2005). Nuclei were isolated from individual clones, treated with DNase I and highsalt extracted as described in Methods.…”

Section: Fr-mar Containing Constructs Are Associated With the Nuclearmentioning

confidence: 99%

A nuclear matrix attachment site in the 4q35 locus has an enhancer-blocking activity in vivo: Implications for the facio-scapulo-humeral dystrophy

Petrov¹,

Allinne²,

Pirozhkova³

et al. 2007

Genome Res.

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Facio-scapulo-humeral dystrophy (FSHD), a muscular hereditary disease with a prevalence of 1 in 20,000, is caused by a partial deletion of a subtelomeric repeat array on chromosome 4q. Earlier, we demonstrated the existence in the vicinity of the D4Z4 repeat of a nuclear matrix attachment site, FR-MAR, efficient in normal human myoblasts and nonmuscular human cells but much weaker in muscle cells from FSHD patients. We now report that the D4Z4 repeat contains an exceptionally strong transcriptional enhancer at its 5′-end. This enhancer up-regulates transcription from the promoter of the neighboring FRG1 gene. However, an enhancer blocking activity was found present in FR-MAR that in vitro could protect transcription from the enhancer activity of the D4Z4 array. In vivo, transcription from the FRG1 and FRG2 genes could be down- or up-regulated depending on whether or not FR-MAR is associated with the nuclear matrix. We propose a model for an etiological role of the delocalization of FR-MAR in the genesis of FSHD.

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Section: Fr-mar Containing Constructs Are Associated With the Nuclearmentioning

confidence: 99%

A nuclear matrix attachment site in the 4q35 locus has an enhancer-blocking activity in vivo: Implications for the facio-scapulo-humeral dystrophy

Petrov¹,

Allinne²,

Pirozhkova³

et al. 2007

Genome Res.

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“…Next we undertook the mapping of the chromatin loop organization in the 250-kb region between D4Z4 repeats and the upstream area of the FRG1 gene in normal myoblasts and in cells from FSHD patients by using genomic DNA arrays. We have used a technique for mapping the interactions of DNA with the nuclear matrix based on oligonucleotide DNA arrays (32). This method allows for rapid and accurate study of S͞MARs over large sequenced areas of various genomes.…”

Section: Mapping the Chromatin Loop Domain At The 4q35 Locus By Usingmentioning

confidence: 99%

“…The oligonucleotides were quantified and slot-blotted onto a nylon membrane as described in ref. 32. As a control, the chosen oligonucleotides in the array were tested for the presence of repetitive DNA by hybridization with total DNA.…”

Section: Mapping the Chromatin Loop Domain At The 4q35 Locus By Usingmentioning

confidence: 99%

Chromatin loop domain organization within the 4q35 locus in facioscapulohumeral dystrophy patients versus normal human myoblasts

Petrov

Pirozhkova

Carnac

et al. 2006

Proc. Natl. Acad. Sci. U.S.A.

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Fascioscapulohumeral muscular dystrophy (FSHD) is an autosomal dominant neuromuscular disorder linked to partial deletion of integral numbers of a 3.3 kb polymorphic repeat, D4Z4, within the subtelomeric region of chromosome 4q. Although the relationship between deletions of D4Z4 and FSHD is well established, how this triggers the disease remains unclear. We have mapped the DNA loop domain containing the D4Z4 repeat cluster in human primary myoblasts and in murine-human hybrids. A nuclear matrix attachment site was found located in the vicinity of the repeat. Prominent in normal human myoblasts and nonmuscular human cells, this site is much weaker in muscle cells derived from FSHD patients, suggesting that the D4Z4 repeat array and upstream genes reside in two loops in nonmuscular cells and normal human myoblasts but in only one loop in FSHD myoblasts. We propose a model whereby the nuclear scaffold͞matrix attached region regulates chromatin accessibility and expression of genes implicated in the genesis of FSHD. The disorder is related to a short repeat array that remains after deletion of an integral number of tandemly arrayed 3.3-kb repeat units on chromosome 4. The size of this polymorphic locus (D4Z4) varies in normal individuals from 35 to 300 kb, whereas in FSHD patients it is consistently shorter than 35 kb (3). Partial deletion of the D4Z4 array on chromosome 4 ultimately leads to FSHD and is currently used as a diagnostic tool in genetic counseling to predict the probability of the disease (1,(3)(4)(5). A correlation exists between the extent of the deletion and its clinical expression: Indeed, patients with one to three repeats develop an early FSHD, whereas individuals with nine to 10 repeats exhibit a weaker form of the disease (5).Extensive efforts to identify gene transcripts associated with the 4q35-specific D4Z4 repeat, as potential FSHD candidate genes, have been largely unsuccessful (6). The 3.3-kb D4Z4 elements contain a cryptic DUX4 gene potentially coding for a double homeodomain protein (7), and an overall perturbation of mRNA expression profiles can be observed in FSHD patients (8-10), but the disease appears to result from an as yet unexplained mechanism with a genetic alteration not residing within a causative gene for the disease.The 4q35 genomic region ( Fig. 1) displays heterochromatic features and might exert repressive effects on neighboring genes with a mechanism similar to position effect variegation. A decreased D4Z4 repeat number consistently results in inappropriate up-regulation of adjacent FRG2, FRG1, and Ant1 in FSHD muscle (11-13). It has also been shown that a transcriptional repressor complex binds D4Z4, whose deletion would trigger overexpression by lack of repression (11). Indeed, overexpression of FRG1 in transgenic mice provokes a phenotype similar to that of FSHD (14). However, such a model of position effect has been recently challenged in two reports of an apparent lack of up-regulation of any 4q35 gene and because of the histone H4 acetylation state in FSHD lymph...

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“…S/MARs anchor chromatin onto the NM, thereby organizing the genomic DNA into topologically distinct loop domains that are important for the regulation of replication and transcription. 2 Despite numerous genomic studies, [3][4][5][6][7] no consensus S/MAR sequence has been identified so far. 8 S/MARs can be both A/T 9 or G/C rich.…”

Section: Introductionmentioning

confidence: 99%

DNA polymorphism and epigenetic marks modulate the affinity of a scaffold/matrix attachment region to the nuclear matrix

et al. 2014

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Mechanisms that regulate attachment of the scaffold/matrix attachment regions (S/MARs) to the nuclear matrix remain largely unknown. We have studied the effect of simple sequence length polymorphism (SSLP), DNA methylation and chromatin organization in an S/MAR implicated in facioscapulohumeral dystrophy (FSHD), a hereditary disease linked to a partial deletion of the D4Z4 repeat array on chromosome 4q. This FSHD-related nuclear matrix attachment region (FR-MAR) loses its efficiency in myoblasts from FSHD patients. Three criteria were found to be important for high-affinity interaction between the FR-MAR and the nuclear matrix: the presence of a specific SSLP haplotype in chromosomal DNA, the methylation of one specific CpG within the FR-MAR and the absence of histone H3 acetylated on lysine 9 in the relevant chromatin fragment.

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Mapping long-range chromatin organization within the chicken α-globin gene domain using oligonucleotide DNA arrays

Cited by 22 publications

References 40 publications

A nuclear matrix attachment site in the 4q35 locus has an enhancer-blocking activity in vivo: Implications for the facio-scapulo-humeral dystrophy

A nuclear matrix attachment site in the 4q35 locus has an enhancer-blocking activity in vivo: Implications for the facio-scapulo-humeral dystrophy

Chromatin loop domain organization within the 4q35 locus in facioscapulohumeral dystrophy patients versus normal human myoblasts

DNA polymorphism and epigenetic marks modulate the affinity of a scaffold/matrix attachment region to the nuclear matrix

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