Chromatin modification of the human imprinted <i>NDN</i> (necdin) gene detected by in vivo footprinting

Hanel, Meredith L.; Lau, Jason C. Y.; Paradis, Isabelle; Drouin, Régen; Wevrick, Rachel

doi:10.1002/jcb.20365

Cited by 5 publications

(5 citation statements)

References 26 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…The upstream SNRPN promoters U1A and U1B also contain potential NRF-1 binding sites; however, no interaction of NRF-1 was detected with either allele of the U1A promoter (Figure 6B), which is not active in blood cells (5). In addition, we have identified by sequence analysis a conserved potential NRF-1 binding site in the NDN promoter region, which coincides with a sequence that is in vivo footprinted on the paternal NDN allele only (43). The fact that NRF-1 may be regulating at least some of the genes in the PWS/AS region is interesting because of the involvement of NRF-1 in the regulation of genes related to mitochondrial biogenesis and function, metabolism (including growth factor receptors and factors involved in glucose homeostasis), DNA replication and transcriptional regulation (26).…”

Section: Discussionmentioning

confidence: 80%

Characterization of cis- and trans-acting elements in the imprinted human SNURF-SNRPN locus

Rodriguez-Jato

Nicholls²,

Driscoll³

et al. 2005

Nucleic Acids Research

View full text Add to dashboard Cite

The imprinted SNRPN locus is a complex transcriptional unit that encodes the SNURF and SmN polypeptides as well as multiple non-coding RNAs. SNRPN is located within the Prader-Willi and Angelman syndrome (PWS/AS) region that contains multiple imprinted genes, which are coordinately regulated by a bipartite imprinting center (IC). The SNRPN 5′ region co-localizes with the PWS-IC and contains two DNase I hypersensitive sites, DHS1 at the SNRPN promoter, and DHS2 within intron 1, exclusively on the paternally inherited chromosome. We have examined DHS1 and DHS2 to identify cis- and trans-acting regulatory elements within the endogenous SNRPN 5′ region. Analysis of DHS1 by in vivo footprinting and chromatin immunoprecipitation identified allele-specific interaction with multiple regulatory proteins, including NRF-1, which regulates genes involved in mitochondrial and metabolic functions. DHS2 acted as an enhancer of the SNRPN promoter and contained a highly conserved region that showed allele-specific interaction with unphosphorylated RNA polymerase II, YY1, Sp1 and NRF-1, further suggesting a key role for NRF-1 in regulation of the SNRPN locus. We propose that one or more of the regulatory elements identified in this study may also contribute to PWS-IC function.

show abstract

Section: Discussionmentioning

confidence: 80%

Characterization of cis- and trans-acting elements in the imprinted human SNURF-SNRPN locus

Rodriguez-Jato

Nicholls²,

Driscoll³

et al. 2005

Nucleic Acids Research

View full text Add to dashboard Cite

show abstract

“…Alternatively, it could reflect the erasure of imprinting in the embryonic genome or simply that the imprint mark had not yet been established. The need for overlapping epigenetic signals has been recognized, including alterations in chromatin configuration [37], and precludes a definitive decision in this matter without additional experimental evidence. Our observation that NDN in ESCs was exclusively expressed from the paternal allele suggests that it was simply a matter of timing and that imprinting had not yet been established in the day‐7 to ‐9 blastocyst.…”

Section: Discussionmentioning

confidence: 99%

Aberrant Genomic Imprinting in Rhesus Monkey Embryonic Stem Cells

et al. 2005

View full text Add to dashboard Cite

Genomic imprinting involves modification of a gene or a chromosomal region that results in the differential expression of parental alleles. Disruption or inappropriate expression of imprinted genes is associated with several clinically significant syndromes and tumorigenesis in humans. Additionally, abnormal imprinting occurs in mouse embryonic stem cells (ESCs) and in clonally derived animals. Imprinted gene expression patterns in primate ESCs are largely unknown, despite the clinical potential of the latter in the cell-based treatment of human disease. Because of the possible implications of abnormal gene expression to cell or tissue replacement therapies involving ESCs, we examined allele specific expression of four imprinted genes in the rhesus macaque. Genomic and complementary DNA from embryos and ESC lines containing useful single nucleotide polymorphisms were subjected to polymerase chain reaction-based amplification and sequence analysis. In blastocysts, NDN expression was variable indicating abnormal or incomplete imprinting whereas IGF2 and SNRPN were expressed exclusively from the paternal allele and H19 from the maternal allele as expected. In ESCs, both NDN and SNRPN were expressed from the paternal allele while IGF2 and H19 showed loss of imprinting and biallelic expression. In differentiated ESC progeny, these expression patterns were maintained. The implications of aberrant imprinted gene expression to ESC differentiation in vitro and on ESCderived cell function in vivo after transplantation are unknown. STEM CELLS 2006;24:595-603

show abstract

“…In our dataset, an example of imprinting is illustrated by the known SNP (rs2192206) in the gene encoding the growth suppressor necdin NDN (Table 3). NDN is known for its exclusively paternal expression [19]; rs2192206 presented with well-balanced heterozygous signal in both exomes and monozygotic expression of the variant allele in both transcriptomes (Figure 2A). In contrast, rs73231013 in the gene encoding the nucleosome binding protein HMGN5 shows similar expression pattern (Figure 2B) without acknowledged involvement of imprinting processes.…”

Section: Resultsmentioning

confidence: 99%

Extraction of Molecular Features through Exome to Transcriptome Alignment

Mudvari

Kowsari

Cole

et al. 2013

J Metabol Syst Biol

View full text Add to dashboard Cite

Integrative Next Generation Sequencing (NGS) DNA and RNA analyses have very recently become feasible, and the published to date studies have discovered critical disease implicated pathways, and diagnostic and therapeutic targets. A growing number of exomes, genomes and transcriptomes from the same individual are quickly accumulating, providing unique venues for mechanistic and regulatory features analysis, and, at the same time, requiring new exploration strategies. In this study, we have integrated variation and expression information of four NGS datasets from the same individual: normal and tumor breast exomes and transcriptomes. Focusing on SNPcentered variant allelic prevalence, we illustrate analytical algorithms that can be applied to extract or validate potential regulatory elements, such as expression or growth advantage, imprinting, loss of heterozygosity (LOH), somatic changes, and RNA editing. In addition, we point to some critical elements that might bias the output and recommend alternative measures to maximize the confidence of findings. The need for such strategies is especially recognized within the growing appreciation of the concept of systems biology: integrative exploration of genome and transcriptome features reveal mechanistic and regulatory insights that reach far beyond linear addition of the individual datasets.

show abstract

Chromatin modification of the human imprinted NDN (necdin) gene detected by in vivo footprinting

Cited by 5 publications

References 26 publications

Characterization of cis- and trans-acting elements in the imprinted human SNURF-SNRPN locus

Characterization of cis- and trans-acting elements in the imprinted human SNURF-SNRPN locus

Aberrant Genomic Imprinting in Rhesus Monkey Embryonic Stem Cells

Extraction of Molecular Features through Exome to Transcriptome Alignment

Contact Info

Product

Resources

About