OCT3/4-binding sequence-dependent maintenance of the unmethylated state of CTCF-binding sequences with DNA demethylation and suppression of de novo DNA methylation in the H19 imprinted control region

Hori, Naohiro; Kubo, Shunsuke; Sakasegawa, Taku; Sakurai, Chiye; Hatsuzawa, Kiyotaka

doi:10.1016/j.gene.2020.144606

Cited by 3 publications

(2 citation statements)

References 35 publications

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“…Point mutations within transcription-factor binding sites at the ICRs of the human IGF2-H19 and KCNQ1 domains have provided evidence for such a scenario as well [110][111][112][113][114]. Conversely, CTCF itself may protect the unmethylated allele against de novo DNA methylation [110,111,115,116], thus ensuring continued transcription of the lncRNA from the unmethylated parental allele only.…”

Section: Emerging Roles Of Imprinted Lncrnas In Chromatin Architecturementioning

confidence: 99%

Exploring chromatin structural roles of non-coding RNAs at imprinted domains

Llères

Imaizumi

Feil

2021

Biochemical Society Transactions

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Different classes of non-coding RNA (ncRNA) influence the organization of chromatin. Imprinted gene domains constitute a paradigm for exploring functional long ncRNAs (lncRNAs). Almost all express an lncRNA in a parent-of-origin dependent manner. The mono-allelic expression of these lncRNAs represses close by and distant protein-coding genes, through diverse mechanisms. Some control genes on other chromosomes as well. Interestingly, several imprinted chromosomal domains show a developmentally regulated, chromatin-based mechanism of imprinting with apparent similarities to X-chromosome inactivation. At these domains, the mono-allelic lncRNAs show a relatively stable, focal accumulation in cis. This facilitates the recruitment of Polycomb repressive complexes, lysine methyltranferases and other nuclear proteins — in part through direct RNA–protein interactions. Recent chromosome conformation capture and microscopy studies indicate that the focal aggregation of lncRNA and interacting proteins could play an architectural role as well, and correlates with close positioning of target genes. Higher-order chromatin structure is strongly influenced by CTCF/cohesin complexes, whose allelic association patterns and actions may be influenced by lncRNAs as well. Here, we review the gene-repressive roles of imprinted non-coding RNAs, particularly of lncRNAs, and discuss emerging links with chromatin architecture.

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Section: Emerging Roles Of Imprinted Lncrnas In Chromatin Architecturementioning

confidence: 99%

Exploring chromatin structural roles of non-coding RNAs at imprinted domains

Llères

Imaizumi

Feil

2021

Biochemical Society Transactions

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“…Pioneering transcription factors, including OCT4 and SOX2, can protect their binding sites from DNA methylation by inducing TET-dependent active DNA demethylation (Hori et al 2020;Vanzan et al 2021). Therefore, TET family proteins may be recruited by OCT4 binding to maternal SOBS in H19-ICR.…”

Section: Discussionmentioning

confidence: 99%

Identification of the sequences responsible for maternalH19-ICR hypermethylation with Beckwith-Wiedemann syndrome-like overgrowth in mice

Hara,

Matsuhisa,

Kitajima

et al. 2024

Preprint

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Beckwith-Wiedemann syndrome (BWS) is caused by a gain of methylation (GOM) at the imprinting control region within theIgf2-H19domain on the maternal allele (H19-ICR GOM). Mutations in the binding sites of several transcription factors are involved inH19-ICR GOM and BWS. However, the responsible sequence(s) forH19-ICR GOM with BWS-like overgrowth has not been identified in mice. Here, we report that a mutation in the SOX-OCT binding site (SOBS) causes partialH19-ICR GOM, which does not extend beyond CTCF binding site 3 (CTS3). Moreover, simultaneously mutating both SOBS and CTS3 causes complete GOM of the entireH19-ICR, leading to the misexpression of the imprinted genes, and frequent BWS-like overgrowth. In addition, CTS3 is critical for CTCF/cohesin-mediated chromatin conformation. These results indicate that SOBS and CTS3 are the sequences responsible forH19-ICR GOM leading to BWS-like overgrowth and are essential for maintaining the unmethylated state of maternalH19-ICR.

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Identification of responsible sequences which mutations cause maternal H19-ICR hypermethylation with Beckwith–Wiedemann syndrome-like overgrowth

Hara,

Matsuhisa,

Kitajima

et al. 2024

Commun Biol

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Beckwith-Wiedemann syndrome (BWS) is caused by a gain of methylation (GOM) at the imprinting control region within the Igf2-H19 domain on the maternal allele (H19-ICR GOM). Mutations in the binding sites of several transcription factors are involved in H19-ICR GOM and BWS. However, the responsible sequence(s) for H19-ICR GOM with BWS-like overgrowth has not been identified in mice. Here, we report that a mutation in the SOX-OCT binding site (SOBS) causes partial H19-ICR GOM, which does not extend beyond CTCF binding site 3 (CTS3). Moreover, simultaneously mutating both SOBS and CTS3 causes complete GOM of the entire H19-ICR, leading to the misexpression of the imprinted genes, and frequent BWS-like overgrowth. In addition, CTS3 is critical for CTCF/cohesin-mediated chromatin conformation. These results indicate that SOBS and CTS3 are the sequences in which mutations cause H19-ICR GOM leading to BWS-like overgrowth and are essential for maintaining the unmethylated state of maternal H19-ICR.

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OCT3/4-binding sequence-dependent maintenance of the unmethylated state of CTCF-binding sequences with DNA demethylation and suppression of de novo DNA methylation in the H19 imprinted control region

Cited by 3 publications

References 35 publications

Exploring chromatin structural roles of non-coding RNAs at imprinted domains

Exploring chromatin structural roles of non-coding RNAs at imprinted domains

Identification of the sequences responsible for maternalH19-ICR hypermethylation with Beckwith-Wiedemann syndrome-like overgrowth in mice

Identification of responsible sequences which mutations cause maternal H19-ICR hypermethylation with Beckwith–Wiedemann syndrome-like overgrowth

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