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

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 bi...

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Bibliographic Details
Published in:Nucleic acids research 2005-01, Vol.33 (15), p.4740-4753
Main Authors: Rodriguez-Jato, Sara, Nicholls, Robert D., Driscoll, Daniel J., Yang, Thomas P.
Format: Article
Language:English
Subjects:
5' Flanking Region
Angelman Syndrome - genetics
Autoantigens
Base Sequence
Binding Sites
Deoxyribonuclease I - metabolism
DNA Footprinting
Enhancer Elements, Genetic
Genomic Imprinting
Histones - metabolism
Humans
Introns
Molecular Sequence Data
Nuclear Proteins - genetics
Prader-Willi Syndrome - genetics
Promoter Regions, Genetic
Response Elements
Ribonucleoproteins, Small Nuclear - genetics
RNA Polymerase II - metabolism
snRNP Core Proteins
Transcription Factors - metabolism
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Summary: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.
ISSN:0305-1048
1362-4962
DOI:10.1093/nar/gki786