Long noncoding RNA-mediated intrachromosomal interactions promote imprinting at the <i>Kcnq1</i> locus

Zhang, He; Zeitz, Μ.; Wang, Hong; Niu, Beibei; Ge, Shengfang; Li, Wei; Cui, Jiuwei; Wang, Guanjun; Qian, Guofeng; Higgins, Michael J.; Fan, Xianqun; Hoffman, Andrew R.; Hu, Ji-Fan

doi:10.1083/jcb.201304152

Cited by 120 publications

(125 citation statements)

References 38 publications

(68 reference statements)

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“…E 2 E3 E 4 E 5 E 6 E7 Enhancer 20 kb Although the MIR31HG transcript binds the genomic regions MIR31HG and INK4A, we could not detect a direct interaction between the two loci using 4C-seq, which in turn rules out a chromatin looping model, as has recently been shown for other lncRNAs 56,57 . In contrast, our 4C-seq, as well as previously published HiC-seq data 58 , indicates that the two genes belong to separate topological domains and therefore are likely to not have physiological relevant interactions.…”

Section: E1mentioning

confidence: 39%

The lncRNA MIR31HG regulates p16INK4A expression to modulate senescence

et al. 2015

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Oncogene-induced senescence (OIS) can occur in response to oncogenic insults and is considered an important tumour suppressor mechanism. Here we identify the lncRNA MIR31HG as upregulated in OIS and find that knockdown of MIR31HG promotes a strong p16 INK4A -dependent senescence phenotype. Under normal conditions, MIR31HG is found in both nucleus and cytoplasm, but following B-RAF expression MIR31HG is located mainly in the cytoplasm. We show that MIR31HG interacts with both INK4A and MIR31HG genomic regions and with Polycomb group (PcG) proteins, and that MIR31HG is required for PcG-mediated repression of the INK4A locus. We further identify a functional enhancer, located between MIR31HG and INK4A, which becomes activated during OIS and interacts with the MIR31HG promoter. Data from melanoma patients show a negative correlation between MIR31HG and p16 INK4A expression levels, suggesting a role for this transcript in cancer. Hence, our data provide a new lncRNA-mediated regulatory mechanism for the tumour suppressor p16 INK4A .

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Section: E1mentioning

confidence: 39%

The lncRNA MIR31HG regulates p16INK4A expression to modulate senescence

et al. 2015

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“…Further studies are needed to shed light on this aspect. This also sets Dum apart from Kcnqu1 ot1 lncRNA which functions as a molecular hinge to link the Kcnq1 promoter and KvDMR1 DNAs together and a scaffold for a long-range intrachromosomal loop [30]. Our results from ChIRP assay also indicated that Dum anchors to Dppa2 CpG regions through directly binding to the two regions identified, suggesting that it acts as a tethering molecule to recruit Dnmts.…”

Section: Discussionmentioning

confidence: 56%

LncRNA Dum interacts with Dnmts to regulate Dppa2 expression during myogenic differentiation and muscle regeneration

et al. 2015

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Emerging studies document the roles of long non-coding RNAs (LncRNAs) in regulating gene expression at chromatin level but relatively less is known how they regulate DNA methylation. Here we identify an lncRNA, Dum (developmental pluripotency-associated 2 (Dppa2) Upstream binding Muscle lncRNA) in skeletal myoblast cells. The expression of Dum is dynamically regulated during myogenesis in vitro and in vivo. It is also transcriptionally induced by MyoD binding upon myoblast differentiation. Functional analyses show that it promotes myoblast differentiation and damage-induced muscle regeneration. Mechanistically, Dum was found to silence its neighboring gene, Dppa2, in cis through recruiting Dnmt1, Dnmt3a and Dnmt3b. Furthermore, intrachromosomal looping between Dum locus and Dppa2 promoter is necessary for Dum/Dppa2 interaction. Collectively, we have identified a novel lncRNA that interacts with Dnmts to regulate myogenesis.

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“…As previously described [25,27], total RNA was extracted from tissues by TRI-REAGENT (Sigma, CA) and cDNA was synthesised with RNA reverse transcriptase. Briefly, 1 lg of total RNA was used, and PCR was carried out under liquid wax in a 6 ll reaction mixture containing 2 ll of 3 Â Klen-Taq I Mix, 2 ll cDNA and 1 ll of each 2.5 lM primer.…”

Section: Reverse Transcription-polymerase Chain Reaction (Pcr) Analysismentioning

confidence: 99%

“…Using a recently-developed R3C (RNA-guided Chromatin Conformation Capture) technique [25], we recently identified a novel long non-coding RNA (lncRNA) IRAIN within the IGF1R locus [26]. IRAIN is transcribed from an intragenic promoter located in the first intron of IGF1R.…”

Section: Introductionmentioning

confidence: 99%

Aberrant allele-switch imprinting of a novel IGF1R intragenic antisense non-coding RNA in breast cancers

Kang

Sun

Xue

et al. 2015

European Journal of Cancer

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Long noncoding RNA-mediated intrachromosomal interactions promote imprinting at the Kcnq1 locus

Abstract: A long noncoding RNA directly builds an intrachromosomal interaction complex to establish allele-specific transcriptional gene silencing over a large chromosomal domain.

Cited by 120 publications

References 38 publications

The lncRNA MIR31HG regulates p16INK4A expression to modulate senescence

The lncRNA MIR31HG regulates p16INK4A expression to modulate senescence

LncRNA Dum interacts with Dnmts to regulate Dppa2 expression during myogenic differentiation and muscle regeneration

Aberrant allele-switch imprinting of a novel IGF1R intragenic antisense non-coding RNA in breast cancers

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