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A novel antisense long noncoding RNA within the IGF1R gene locus is imprinted in hematopoietic malignancies.

Sun J, Li W, Sun Y, Yu D, Wen X, Wang H, Cui J, Wang G, Hoffman AR, Hu JF - Nucleic Acids Res. (2014)

Bottom Line: Using both reverse transcription-associated trap and chromatin conformation capture assays, we demonstrate that this lncRNA interacts with chromatin DNA and is involved in the formation of an intrachromosomal enhancer/promoter loop.In addition, IRAIN was downregulated both in leukemia cell lines and in blood obtained from high-risk AML patients.These data identify IRAIN as a new imprinted lncRNA that is involved in long-range DNA interactions.

View Article: PubMed Central - PubMed

Affiliation: Stem Cell and Cancer Center, First Affiliated Hospital, Jilin University, Changchun, Jilin 130061, PR China Stanford University Medical School, VA Palo Alto Health Care System, Palo Alto, CA 94304, USA.

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The IRAIN lncRNA is imprinted in hematopoietic cells. (A) Polymorphic restriction enzymes used to distinguish the two parental alleles. SNP: single nucleotide polymorphism. The IRAIN lncRNA was reverse transcribed into cDNA using SSRT oligonucleotides. The PCR products were digested by polymorphic Alu I and Sac II. (B and C) Allelic expression of IRAIN lncRNA at the E site in KG-1 and KG-1a leukemia cells. gDNA: heterozygous genomic DNA. Note the single ‘A’ allele or the single ‘G’ allele expression of IRAIN lncRNA. (D) Parental imprinting of IRAIN lncRNA by tracking allelic expression in three families. Genomic DNA and cDNA were amplified from peripheral blood cells and the PCR products were sequenced for the A/G alleles. Note the monoallelic expression of IRAIN lncRNA from the paternal allele.
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Figure 2: The IRAIN lncRNA is imprinted in hematopoietic cells. (A) Polymorphic restriction enzymes used to distinguish the two parental alleles. SNP: single nucleotide polymorphism. The IRAIN lncRNA was reverse transcribed into cDNA using SSRT oligonucleotides. The PCR products were digested by polymorphic Alu I and Sac II. (B and C) Allelic expression of IRAIN lncRNA at the E site in KG-1 and KG-1a leukemia cells. gDNA: heterozygous genomic DNA. Note the single ‘A’ allele or the single ‘G’ allele expression of IRAIN lncRNA. (D) Parental imprinting of IRAIN lncRNA by tracking allelic expression in three families. Genomic DNA and cDNA were amplified from peripheral blood cells and the PCR products were sequenced for the A/G alleles. Note the monoallelic expression of IRAIN lncRNA from the paternal allele.

Mentions: The expression pattern of the IGF1R/IRAIN locus is quite similar to the Igf2r/Airn imprinting locus in the mouse, where Airn is imprinted and the lncRNA Airn regulates in cis the allelic expression of the Igf2r coding RNA (43–46). We therefore examined if IRAIN uses a similar epigenetic mechanism to regulate genes. We first examined if IRAIN was monoallelically expressed in tissues. After screening several single nucleotide polymorphisms (SNPs) within the IRAIN locus, we took advantage of polymorphic Alu I and Sac II sites to examine allelic expression of the IRAIN lncRNA (Figure 2A).


A novel antisense long noncoding RNA within the IGF1R gene locus is imprinted in hematopoietic malignancies.

Sun J, Li W, Sun Y, Yu D, Wen X, Wang H, Cui J, Wang G, Hoffman AR, Hu JF - Nucleic Acids Res. (2014)

The IRAIN lncRNA is imprinted in hematopoietic cells. (A) Polymorphic restriction enzymes used to distinguish the two parental alleles. SNP: single nucleotide polymorphism. The IRAIN lncRNA was reverse transcribed into cDNA using SSRT oligonucleotides. The PCR products were digested by polymorphic Alu I and Sac II. (B and C) Allelic expression of IRAIN lncRNA at the E site in KG-1 and KG-1a leukemia cells. gDNA: heterozygous genomic DNA. Note the single ‘A’ allele or the single ‘G’ allele expression of IRAIN lncRNA. (D) Parental imprinting of IRAIN lncRNA by tracking allelic expression in three families. Genomic DNA and cDNA were amplified from peripheral blood cells and the PCR products were sequenced for the A/G alleles. Note the monoallelic expression of IRAIN lncRNA from the paternal allele.
© Copyright Policy - creative-commons
Related In: Results  -  Collection

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getmorefigures.php?uid=PMC4150754&req=5

Figure 2: The IRAIN lncRNA is imprinted in hematopoietic cells. (A) Polymorphic restriction enzymes used to distinguish the two parental alleles. SNP: single nucleotide polymorphism. The IRAIN lncRNA was reverse transcribed into cDNA using SSRT oligonucleotides. The PCR products were digested by polymorphic Alu I and Sac II. (B and C) Allelic expression of IRAIN lncRNA at the E site in KG-1 and KG-1a leukemia cells. gDNA: heterozygous genomic DNA. Note the single ‘A’ allele or the single ‘G’ allele expression of IRAIN lncRNA. (D) Parental imprinting of IRAIN lncRNA by tracking allelic expression in three families. Genomic DNA and cDNA were amplified from peripheral blood cells and the PCR products were sequenced for the A/G alleles. Note the monoallelic expression of IRAIN lncRNA from the paternal allele.
Mentions: The expression pattern of the IGF1R/IRAIN locus is quite similar to the Igf2r/Airn imprinting locus in the mouse, where Airn is imprinted and the lncRNA Airn regulates in cis the allelic expression of the Igf2r coding RNA (43–46). We therefore examined if IRAIN uses a similar epigenetic mechanism to regulate genes. We first examined if IRAIN was monoallelically expressed in tissues. After screening several single nucleotide polymorphisms (SNPs) within the IRAIN locus, we took advantage of polymorphic Alu I and Sac II sites to examine allelic expression of the IRAIN lncRNA (Figure 2A).

Bottom Line: Using both reverse transcription-associated trap and chromatin conformation capture assays, we demonstrate that this lncRNA interacts with chromatin DNA and is involved in the formation of an intrachromosomal enhancer/promoter loop.In addition, IRAIN was downregulated both in leukemia cell lines and in blood obtained from high-risk AML patients.These data identify IRAIN as a new imprinted lncRNA that is involved in long-range DNA interactions.

View Article: PubMed Central - PubMed

Affiliation: Stem Cell and Cancer Center, First Affiliated Hospital, Jilin University, Changchun, Jilin 130061, PR China Stanford University Medical School, VA Palo Alto Health Care System, Palo Alto, CA 94304, USA.

Show MeSH
Related in: MedlinePlus