Meg3-DMR，而非 Meg3 基因，调控 Dlk1-Dio3 基因座的印迹。
Meg3-DMR, not the Meg3 gene, regulates imprinting of the Dlk1-Dio3 locus.
机构信息
Neuroendocrine Unit, Massachusetts General Hospital and Harvard Medical Shcool, Boston, MA 02114, USA.
Nephrology Division, Massachusetts General Hospital and Harvard Medical School, Boston, MA, 02114, USA.
出版信息
Dev Biol. 2019 Nov 1;455(1):10-18. doi: 10.1016/j.ydbio.2019.07.005. Epub 2019 Jul 10.
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: Meg3 and Meg3, respectively targeting exons 1-4 and exons 2-4 of the Meg3 gene. A maternal deletion of Meg3 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 Meg3 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.
印记的 delta 样 1 同源物 (DLK1)-甲状腺素脱碘酶 III 型 (DIO3) 基因座调节发育和生长。其印迹调控涉及两个差异甲基化区域 (DMRs)，基因间-DMR (IG-DMR) 和母源表达基因 3-DMR (Meg3-DMR)。在小鼠中，IG-DMR 的母体缺失导致该基因座的 LOI，证明 IG-DMR 是该基因座的顺式作用印迹调控区域。然而，Meg3-DMR 与 Meg3 基因的启动子、外显子 1 和内含子 1 重叠。由于 Meg3-DMR 的缺失使 Meg3 基因失活，因此它们在 Meg3-DMR 小鼠印迹调控中的作用尚不清楚。因此，我们分别生成了两种小鼠模型：Meg3 和 Meg3，分别靶向 Meg3 基因的外显子 1-4 和外显子 2-4。Meg3 的母体缺失导致胚胎和胎盘的胚胎死亡和 LOI，但不影响 IG-DMR 的甲基化状态。相比之下，携带 Meg3 母体缺失的小鼠正常出生且没有 LOI。这些数据表明，是 Meg3-DMR，而不是 Meg3 基因，调节 Dlk1-Dio3 基因座的印迹。
Zotero 插件