Open AccessProtein-binding elements establish in the oocyte the primary imprint of the Prader-Willi/Angelman syndromes domain
Author(s) -
Yotam Kaufman,
Maya Heled,
Jonathan Perk,
Aharon Razin,
Ruth Shemer
Publication year - 2009
Publication title -
proceedings of the national academy of sciences of the united states of america
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.011
H-Index - 771
eISSN - 1091-6490
pISSN - 0027-8424
DOI - 10.1073/pnas.0902087106
Subject(s) - oocyte , methylation , genomic imprinting , biology , epigenetics , imprinting (psychology) , genetics , dna methylation , microbiology and biotechnology , gene , embryo , gene expression
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.