Protein-binding elements establish in the oocyte the primary imprint of the Prader-Willi/Angelman syndromes domain
- 23 June 2009
- journal article
- Published by Proceedings of the National Academy of Sciences in Proceedings of the National Academy of Sciences of the United States of America
- Vol. 106 (25), 10242-10247
- https://doi.org/10.1073/pnas.0902087106
Abstract
Imprinting of the PWS/AS 2.4 Mb domain in the human is controlled by a paternally active imprinting center (PWS-IC). PWS-IC on the maternal allele is methylated and inactivated by an 880-bp sequence (AS-IC) located 30 kb upstream. In this communication, we report the identification of 7 cis acting elements within AS-IC. The elements: DMR, DNS, 2 OCTA sequences, SOX, E1, and E2 bind specific proteins that form at least 2 protein complexes. Using variants of an imprinted transgene, mutated at the elements each at a time, we show that (i) all 7 elements are involved in the methylation and inactivation of the maternal PWS-IC; (ii) the OCTA and SOX elements that bind a protein complex, and the E1 and E2 elements, function in establishing the primary imprint that constitutes an active and unmethylated AS-IC in the oocyte; (iii) DNS and DMR bind a multiprotein complex that may facilitate interaction between AS-IC and PWS-IC, mediating the inactivation in cis of PWS-IC; and (iv) all 7 elements participate in maintaining an unmethylated PWS-IC in the oocyte, which is essential for its maternal methylation later in development. Altogether, the above observations imply that the cis acting elements on AS-IC display diverse functions in establishing the imprints at both AS-IC and PWS-IC in the oocyte. A postulated epigenetic mark imprints the PWS-IC in the oocyte and maintains its inactive status during development before it is translated into maternal methylation.Keywords
This publication has 32 references indexed in Scilit:
- Transcription is required for establishment of germline methylation marks at imprinted genesGenes & Development, 2009
- De novo DNA methylation promoted by G9a prevents reprogramming of embryonically silenced genesNature Structural & Molecular Biology, 2008
- Maternal Oct-4 is a potential key regulator of the developmental competence of mouse oocytesBMC Developmental Biology, 2008
- A Maternal-Zygotic Effect Gene, Zfp57, Maintains Both Maternal and Paternal ImprintsDevelopmental Cell, 2008
- Control elements within the PWS/AS imprinting box and their function in the imprinting processHuman Molecular Genetics, 2004
- Methylation imprints of the imprint control region of the SNRPN-gene in human gametes and preimplantation embryosHuman Molecular Genetics, 2003
- Role of Histone Methyltransferase G9a in CpG Methylation of the Prader-Willi Syndrome Imprinting CenterPublished by Elsevier BV ,2003
- A 5-kb imprinting center deletion in a family with Angelman syndrome reduces the shortest region of deletion overlap to 880 bpHuman Genetics, 1999
- Imprint switching on human chromosome 15 may involve alternative transcripts of the SNRPN geneNature Genetics, 1996
- A small-scale procedure for preparation of nuclear extracts that support efficient transcription and pre-mRNA splicingGene Analysis Techniques, 1988