Meg3-DMR, not the Meg3 gene, regulates imprinting of the Dlk1-Dio3 locus
| Autor: | Yanfei Mao, Rachel Kery, Anli Yang, Erin M. Botticelli, Roy J. Soberman, Wende Zhu, Xianling Wang, Xin Wang, Xun Zhang, Jie Zhou, Anne Klibanski, Yunli Zhou |
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| Rok vydání: | 2019 |
| Předmět: |
Male
Placenta Embryonic Development Mice Transgenic Locus (genetics) Biology Iodide Peroxidase Article Genomic Imprinting 03 medical and health sciences Exon 0302 clinical medicine Pregnancy Animals Imprinting (psychology) Molecular Biology Gene Sequence Deletion 030304 developmental biology Mice Knockout Genetics MEG3 Mice Inbred BALB C 0303 health sciences Calcium-Binding Proteins Gene Expression Regulation Developmental Exons Cell Biology DNA Methylation Mice Inbred C57BL Differentially methylated regions DLK1 Genetic Loci Mice Inbred DBA embryonic structures Female RNA Long Noncoding Genomic imprinting 030217 neurology & neurosurgery Developmental Biology |
| Zdroj: | Dev Biol |
| ISSN: | 0012-1606 |
| Popis: | The imprinted delta like 1 homolog (DLK1) - thyroxine deiodinase type III (DIO3) locus regulates development and growth. Its imprinting regulation involves two differentially methylated regions (DMRs), intergenic-DMR (IG-DMR) and maternally expressed gene 3-DMR (Meg3-DMR). In mice, a maternal deletion of the IG-DMR leads to LOI in the locus, proving that the IG-DMR is a cis-acting imprinting control region of the locus. However, the Meg3-DMR overlaps with the promoter, exon 1 and intron 1 of the Meg3 gene. Because deletion of the Meg3-DMR inactivates the Meg3 gene, their roles in imprinting regulation of Meg3-DMR mice is unknown. Therefore, we generated two mouse models: Meg3Δ(1-4) and Meg3Δ(2-4), respectively targeting exons 1–4 and exons 2–4 of the Meg3 gene. A maternal deletion of Meg3Δ(1-4) caused embryonic death and LOI in both embryos and placentas, but did not affect methylation status of the IG-DMR. In contrast, mice carrying a maternal deletion of Meg3Δ(2-4) were born normally and did not have LOI. These data indicate that it is the Meg3-DMR, not the Meg3 gene, which regulates imprinting of the Dlk1-Dio3 locus. |
| Databáze: | OpenAIRE |
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