Unstable transmission of the RS447 human megasatellite tandem repetitive sequence that contains the USP17 deubiquitinating enzyme gene

Okada, Takeya; Gondo, Yoichi; Goto, Jun; Kanazawa, Ichiro; Hadano, Shinji; Ikeda, Joh‐E

doi:10.1007/s00439-002-0698-2

Cited by 31 publications

(30 citation statements)

References 45 publications

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“…Likewise, USP41 is also absent in rat and mouse but present in the human lineage. The rat genome, as previously described for mouse, also lacks true orthologs of human USP17 and USP-17-like sequences encoded within highly polymorphic and tandemly repeated intronless regions located at 4p15 and 8p23 (Okada et al 2002). The closest relatives of USP17 genes in the rat genome are those coding for proteins called DUBs (deubiquitinating enzymes), a group of cytokine-inducible cysteine proteases produced by lymphocytes (Baek et al 2001).…”

Section: Cysteine Proteasesmentioning

confidence: 94%

A Genomic Analysis of Rat Proteases and Protease Inhibitors

Puente¹,

2004

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Proteases perform important roles in multiple biological and pathological processes. The availability of the rat genome sequence has facilitated the analysis of the complete protease repertoire or degradome of this model organism. The rat degradome consists of at least 626 proteases and homologs, which are distributed into 24 aspartic, 160 cysteine, 192 metallo, 221 serine, and 29 threonine proteases. This distribution is similar to that of the mouse degradome but is more complex than that of the human degradome composed of 561 proteases and homologs. This increased complexity of rat proteases mainly derives from the expansion of several families, including placental cathepsins, testases, kallikreins, and hematopoietic serine proteases, involved in reproductive or immunological functions. These protease families have also evolved differently in rat and mouse and may contribute to explain some functional differences between these closely related species. Likewise, genomic analysis of rat protease inhibitors has shown some differences with mouse protease inhibitors and the expansion of families of cysteine and serine protease inhibitors in rodents with respect to human. These comparative analyses may provide new views on the functional diversity of proteases and inhibitors and contribute to the development of innovative strategies for treating proteolysis diseases.

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Section: Cysteine Proteasesmentioning

confidence: 94%

A Genomic Analysis of Rat Proteases and Protease Inhibitors

Puente¹,

2004

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“…Length dependent instability has also been observed for larger repetitive elements, such as the CEB1, B6.7 minisatellites or the 4.7-kb RS447 repeat (Okada et al, 2002). However, unlike TNRs, no threshold length for instability exists for minisatellites, as even five CEB1 units are associated with instability (Buard et al, 1998).…”

Section: Repeat Sequence Tract Length and Purity As Cis-elementsmentioning

confidence: 99%

The contribution of <i>cis</i>-elements to disease-associated repeat instability: clinical and experimental evidence

Cleary

Pearson²

2003

Cytogenet Genome Res

126

132

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Alterations in the length (instability) of gene-specific microsatellites and minisatellites are associated with at least 35 human diseases. This review will discuss the various cis-elements that contribute to repeat instability, primarily through examination of the most abundant disease-associated repetitive element, trinucleotide repeats. For the purpose of this review, we define cis-elements to include the sequence of the repeat units, the length and purity of the repeat tracts, the sequences flanking the repeat, as well as the surrounding epigenetic environment, including DNA methylation and chromatin structure. Gender-, tissue-, developmental- and locus-specific cis-elements in conjunction with trans-factors may facilitate instability through the processes of DNA replication, repair and/or recombination. Here we review the available human data that supports the involvement of cis-elements in repeat instability with limited reference to model systems. In diverse tissues at different developmental times and at specific loci, repetitive elements display variable levels of instability, suggesting vastly different mechanisms may be responsible for repeat instability amongst the disease loci and between various tissues.

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“…The function of macrosatellites is unclear, although RS447 contains an open reading frame coding for a novel deubiquitinating enzyme (Saitoh et al 2000). Although RS447 shows significant meiotic instability (Okada et al 2002), no biological significance for low or high copy number has been determined. However, contraction in the size of the D4Z4 array is associated with facioscapulohumeral muscular dystrophy (Wijmenga et al 1992), indicating that these sequences are not simply "junk" DNA (Ohno 1972), but are integral to genome function.…”

mentioning

confidence: 99%

DXZ4 chromatin adopts an opposing conformation to that of the surrounding chromosome and acquires a novel inactive X-specific role involving CTCF and antisense transcripts

Chadwick¹

2008

Genome Res.

104

204

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Macrosatellite DNA is composed of large repeat units, arranged in tandem over hundreds of kilobases. The macrosatellite repeat DXZ4, localized at Xq23-24, consists of 50–100 copies of a CpG-rich 3-kb monomer. Here I report that on the active X chromosome (Xa), DXZ4 is organized into constitutive heterochromatin characterized by a highly organized pattern of H3K9me3. DXZ4 is expressed from both strands and generates an antisense transcript that is processed into small RNAs that directly correlate with H3K9me3 nucleosomes. In contrast, on the inactive X chromosome (Xi) a proportion of DXZ4 is packaged into euchromatin characterized by H3K4me2 and H3K9Ac. The Xi copy of DXZ4 is bound by the chromatin insulator, CTCF, within a sequence that unidirectionally blocks enhancer–promoter communication. Immediately adjacent to the CTCF-binding site is a bidirectional promoter that, like the sequence flanking the CTCF-binding region, is completely devoid of CpG methylation on the Xi. As on the Xa, both strands are expressed, but longer antisense transcripts can be detected in addition to the processed small RNAs. The euchromatic organization of DXZ4 on the otherwise heterochromatic Xi, its binding of CTCF, and its function as a unidirectional insulator suggest that this macrosatellite has acquired a novel function unique to the process of X chromosome inactivation.

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Unstable transmission of the RS447 human megasatellite tandem repetitive sequence that contains the USP17 deubiquitinating enzyme gene

Cited by 31 publications

References 45 publications

A Genomic Analysis of Rat Proteases and Protease Inhibitors

A Genomic Analysis of Rat Proteases and Protease Inhibitors

The contribution of <i>cis</i>-elements to disease-associated repeat instability: clinical and experimental evidence

DXZ4 chromatin adopts an opposing conformation to that of the surrounding chromosome and acquires a novel inactive X-specific role involving CTCF and antisense transcripts

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