Transcription is required to establish maternal imprinting at the Prader-Willi syndrome and Angelman syndrome locus.

Transcription is required to establish maternal imprinting at the Prader-Willi syndrome and Angelman syndrome locus.

Blog Article

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 Clove 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 Pattern Sheets 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.