A 210-kb Segment of Tandem Repeats and Retroelements Located between Imprinted Subdomains of Mouse Distal Chromosome 7

Shirohzu, Hisao; Yokomine, Takaaki; Sato, Chiyoko; Kato, Reiko; Toyoda, Atsushi; Purbowasito, Wahyu; Suda, Chikako; Mukai, Tsunehiro; Hattori, Masahira; Okumura, Katsuhiko; Sakaki, Yoshiyuki; Sasaki, Hidetada

doi:10.1093/dnares/11.5.325

Cited by 16 publications

(18 citation statements)

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“…Deletion of 260 kb of the Begain-Dlk1 LINE-1 repeat array A large intergenic repeat cluster containing tandem repeat and retroelements has previously been reported between the Igf2/H19 and Kcnq1 imprinted domains; it has been proposed that this cluster may act as a target for epigenetic modifications that regulate imprinting (Shirohzu et al 2004). To investigate whether the recently evolved, long, dense, lamina-associated LINE-1 array in the Dlk1/Dio3 domain might have an impact upon imprinting and gene regulation, it was subjected to targeted deletion by homologous recombination in embryonic stem (ES) cells using vectors from the Mutagenic Insertion and Chromosome Engineering Resource (MICER) (Adams et al 2004).…”

Section: Characterization Of Line-1 Repeat Array In the Dlk1-dio3 Impmentioning

confidence: 99%

Targeted deletion of a 170-kb cluster of LINE-1 repeats and implications for regional control

et al. 2018

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Approximately half the mammalian genome is composed of repetitive sequences, and accumulating evidence suggests that some may have an impact on genome function. Here, we characterized a large array class of repeats of long-interspersed elements (LINE-1). Although widely distributed in mammals, locations of such arrays are species specific. Using targeted deletion, we asked whether a 170-kb LINE-1 array located at a mouse imprinted domain might function as a modulator of local transcriptional control. The LINE-1 array is lamina associated in differentiated ES cells consistent with its AT-richness, and although imprinting occurs both proximally and distally to the array, active LINE-1 transcripts within the tract are biallelically expressed. Upon deletion of the array, no perturbation of imprinting was observed, and abnormal phenotypes were not detected in maternal or paternal heterozygous or homozygous mutant mice. The array does not shield nonimprinted genes in the vicinity from local imprinting control. Reduced neural expression of protein-coding genes observed upon paternal transmission of the deletion is likely due to the removal of a brain-specific enhancer embedded within the LINE array. Our findings suggest that presence of a 170-kb LINE-1 array reflects the tolerance of the site for repeat insertion rather than an important genomic function in normal development.

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Section: Characterization Of Line-1 Repeat Array In the Dlk1-dio3 Impmentioning

confidence: 99%

Targeted deletion of a 170-kb cluster of LINE-1 repeats and implications for regional control

et al. 2018

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“…However, notable differences also exist. In mouse, the region between Th and Ins2 is over 200 kb and contains an extraordinarily high concentration of tandem repeats, long interspersed nuclear element (LINE) retrotransposons and endogenous retroelements (Shirohzu et al, 2004). This repeat-rich region also exhibits asynchronous replication, similar to the rest of the domain, and contains 18 matrix attachment regions (Yatsuki et al, 2000;Purbowasito et al, 2004).…”

Section: Kcnq1ot1 Length and Functionmentioning

confidence: 99%

“…In human, the distance between TH and INS is considerably shorter (~10 kb). However, a highly repetitive region that is enriched for LINEs and SINEs (short interspersed elements) and retroelements is found between ASCL2 and TH (a ~115 kb region) in humans (Shirohzu et al, 2004) and in the marsupial tammar wallaby (Ager et al, 2008). If repetitive regions play a role in boundary function, this might indicate that the boundary between the KCNQ1OT1 and H19 domains in humans is within the ASCL2 and TH repetitive region.…”

Section: Kcnq1ot1 Length and Functionmentioning

confidence: 99%

Depletion of Kcnq1ot1 non-coding RNA does not affect imprinting maintenance in stem cells

et al. 2011

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SUMMARYTo understand the complex regulation of genomic imprinting it is important to determine how early embryos establish imprinted gene expression across large chromosomal domains. Long non-coding RNAs (ncRNAs) have been associated with the regulation of imprinting domains, yet their function remains undefined. Here, we investigated the mouse Kcnq1ot1 ncRNA and its role in imprinted gene regulation during preimplantation development by utilizing mouse embryonic and extra-embryonic stem cell models. Our findings demonstrate that the Kcnq1ot1 ncRNA extends 471 kb from the transcription start site. This is significant as it raises the possibility that transcription through downstream genes might play a role in their silencing, including Th, which we demonstrate possesses maternal-specific expression during early development. To distinguish between a functional role for the transcript and properties inherent to transcription of long ncRNAs, we employed RNA interference-based technology to deplete Kcnq1ot1 transcripts. We hypothesized that post-transcriptional depletion of Kcnq1ot1 ncRNA would lead to activation of normally maternal-specific protein-coding genes on the paternal chromosome. Post-transcriptional short hairpin RNA-mediated depletion in embryonic stem, trophoblast stem and extra-embryonic endoderm stem cells had no observable effect on the imprinted expression of genes within the domain, or on Kcnq1ot1 imprinting center DNA methylation, although a significant decrease in Kcnq1ot1 RNA signal volume in the nucleus was observed. These data support the argument that it is the act of transcription that plays a role in imprint maintenance during early development rather than a post-transcriptional role for the RNA itself.

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“…We recently reported a 0.6-Mb mouse sequence corresponding to this sequence (Shirohzu et al 2004). Comparisons of the two sequences revealed that the gene order and transcriptional polarities are conserved except that two genes/transcripts are missing in chickens (see below).…”

Section: Isolation and Sequencing Of Chicken Bac Clonesmentioning

confidence: 99%

Structural and functional analysis of a 0.5-Mb chicken region orthologous to the imprinted mammalianAscl2/Mash2–Igf2–H19region

Yokomine¹,

Shirohzu²,

Purbowasito³

et al. 2004

Genome Res.

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Previous studies revealed that Igf2 and Mpr/Igf2r are imprinted in eutherian mammals and marsupials but not in monotremes or birds. Igf2 lies in a large imprinted cluster in eutherians, and its imprinting is regulated by long-range mechanisms. As a step to understand how the imprinted cluster evolved, we have determined a 490-kb chicken sequence containing the orthologs of mammalian Ascl2/Mash2, Ins2 and Igf2. We found that most of the genes in this region are conserved between chickens and mammals, maintaining the same transcriptional polarities and exon-intron structures. However, H19, an imprinted noncoding transcript, was absent from the chicken sequence. Chicken ASCL2/CASH4 and INS, the orthologs of the imprinted mammalian genes, showed biallelic expression, further supporting the notion that imprinting evolved after the divergence of mammals and birds. The H19 imprinting center and many of the local regulatory elements identified in mammals were not found in chickens. Also, a large segment of tandem repeats and retroelements identified between the two imprinted subdomains in mice was not found in chickens. Our findings show that the imprinted genes were clustered before the emergence of imprinting and that the elements associated with imprinting probably evolved after the divergence of mammals and birds.

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A 210-kb Segment of Tandem Repeats and Retroelements Located between Imprinted Subdomains of Mouse Distal Chromosome 7

Cited by 16 publications

References 0 publications

Targeted deletion of a 170-kb cluster of LINE-1 repeats and implications for regional control

Targeted deletion of a 170-kb cluster of LINE-1 repeats and implications for regional control

Depletion of Kcnq1ot1 non-coding RNA does not affect imprinting maintenance in stem cells

Structural and functional analysis of a 0.5-Mb chicken region orthologous to the imprinted mammalianAscl2/Mash2–Igf2–H19region

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