Transcription is required to establish maternal imprinting at the Prader-Willi syndrome and Angelman syndrome locus.
The Prader-Willi syndrome (PWS [MIM 17620]) and Angelman syndrome (AS [MIM 105830]) locus is controlled by a bipartite imprinting center (IC) consisting of the PWS-IC and the AS-IC. The most widely accepted model of IC function proposes that the PWS-IC activates gene expression from the paternal all...
| Main Authors: | , , , , |
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2011-12-01
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| Series: | PLoS Genetics |
| Online Access: | http://europepmc.org/articles/PMC3248558?pdf=render |
| _version_ | 1819268203967152128 |
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| author | Emily Y Smith Christopher R Futtner Stormy J Chamberlain Karen A Johnstone James L Resnick |
| author_facet | Emily Y Smith Christopher R Futtner Stormy J Chamberlain Karen A Johnstone James L Resnick |
| author_sort | Emily Y Smith |
| collection | DOAJ |
| description | The Prader-Willi syndrome (PWS [MIM 17620]) and Angelman syndrome (AS [MIM 105830]) locus is controlled by a bipartite imprinting center (IC) consisting of the PWS-IC and the AS-IC. The most widely accepted model of IC function proposes that the PWS-IC activates gene expression from the paternal allele, while the AS-IC acts to epigenetically inactivate the PWS-IC on the maternal allele, thus silencing the paternally expressed genes. Gene order and imprinting patterns at the PWS/AS locus are well conserved from human to mouse; however, a murine AS-IC has yet to be identified. We investigated a potential regulatory role for transcription from the Snrpn alternative upstream exons in silencing the maternal allele using a murine transgene containing Snrpn and three upstream exons. This transgene displayed appropriate imprinted expression and epigenetic marks, demonstrating the presence of a functional AS-IC. Transcription of the upstream exons from the endogenous locus correlates with imprint establishment in oocytes, and this upstream exon expression pattern was conserved on the transgene. A transgene bearing targeted deletions of each of the three upstream exons exhibited loss of imprinting upon maternal transmission. These results support a model in which transcription from the Snrpn upstream exons directs the maternal imprint at the PWS-IC. |
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| id | doaj.art-018093a7b8d946a0a8ba44364d3deba4 |
| institution | Directory Open Access Journal |
| issn | 1553-7390 1553-7404 |
| language | English |
| last_indexed | 2024-12-23T21:29:20Z |
| publishDate | 2011-12-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS Genetics |
| spelling | doaj.art-018093a7b8d946a0a8ba44364d3deba42022-12-21T17:30:30ZengPublic Library of Science (PLoS)PLoS Genetics1553-73901553-74042011-12-01712e100242210.1371/journal.pgen.1002422Transcription is required to establish maternal imprinting at the Prader-Willi syndrome and Angelman syndrome locus.Emily Y SmithChristopher R FuttnerStormy J ChamberlainKaren A JohnstoneJames L ResnickThe Prader-Willi syndrome (PWS [MIM 17620]) and Angelman syndrome (AS [MIM 105830]) locus is controlled by a bipartite imprinting center (IC) consisting of the PWS-IC and the AS-IC. The most widely accepted model of IC function proposes that the PWS-IC activates gene expression from the paternal allele, while the AS-IC acts to epigenetically inactivate the PWS-IC on the maternal allele, thus silencing the paternally expressed genes. Gene order and imprinting patterns at the PWS/AS locus are well conserved from human to mouse; however, a murine AS-IC has yet to be identified. We investigated a potential regulatory role for transcription from the Snrpn alternative upstream exons in silencing the maternal allele using a murine transgene containing Snrpn and three upstream exons. This transgene displayed appropriate imprinted expression and epigenetic marks, demonstrating the presence of a functional AS-IC. Transcription of the upstream exons from the endogenous locus correlates with imprint establishment in oocytes, and this upstream exon expression pattern was conserved on the transgene. A transgene bearing targeted deletions of each of the three upstream exons exhibited loss of imprinting upon maternal transmission. These results support a model in which transcription from the Snrpn upstream exons directs the maternal imprint at the PWS-IC.http://europepmc.org/articles/PMC3248558?pdf=render |
| spellingShingle | Emily Y Smith Christopher R Futtner Stormy J Chamberlain Karen A Johnstone James L Resnick Transcription is required to establish maternal imprinting at the Prader-Willi syndrome and Angelman syndrome locus. PLoS Genetics |
| title | Transcription is required to establish maternal imprinting at the Prader-Willi syndrome and Angelman syndrome locus. |
| title_full | Transcription is required to establish maternal imprinting at the Prader-Willi syndrome and Angelman syndrome locus. |
| title_fullStr | Transcription is required to establish maternal imprinting at the Prader-Willi syndrome and Angelman syndrome locus. |
| title_full_unstemmed | Transcription is required to establish maternal imprinting at the Prader-Willi syndrome and Angelman syndrome locus. |
| title_short | Transcription is required to establish maternal imprinting at the Prader-Willi syndrome and Angelman syndrome locus. |
| title_sort | transcription is required to establish maternal imprinting at the prader willi syndrome and angelman syndrome locus |
| url | http://europepmc.org/articles/PMC3248558?pdf=render |
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