{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nRecent studies have established that the imprinted gene cluster encompassing Gpr1 and Zdbf2 plays a critical role in orchestrating early developmental transcriptional programs through tightly regulated, parent‐of‐origin specific epigenetic modifications. In mouse and human models, a paternally expressed Zdbf2 transcript is generated under the influence of a germline differentially methylated region (DMR) that is established during gametogenesis. This imprinting, initially involving a maternally derived mark that is transient in the pluripotent embryo, permits the expression of a long isoform (Liz) that functions both as a protein‐coding RNA and as a cis‐regulatory transcript to prime the later canonical Zdbf2 expression."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": " \n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nFurther epigenomic analyses using methylated-DNA immunoprecipitation-on-chip revealed that the DMR at the Zdbf2 locus is unusually extensive and structured in a tripartite manner, with its methylation status relying on de novo methyltransferase activity. These findings corroborated the imprinted, paternally methylated status of the domain and the adjacent Gpr1 gene – emphasizing a coordinated regulation within the cluster."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "3"}]}, {"type": "t", "text": " \n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nA novel long intergenic non-coding RNA transcript, Zdbf2linc, was identified as being paternally expressed from the Gpr1 DMR during early embryogenesis. Although its expression is largely confined to early developmental stages, Zdbf2linc appears to influence the establishment of secondary epigenetic modifications that ensure the precise, monoallelic activation of the canonical Zdbf2 promoter later in development."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "4"}]}, {"type": "t", "text": " \n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nFinally, functional studies in mouse models have demonstrated that an accurate dosage of Zdbf2 is essential for vital physiological processes at the perinatal stage. Loss-of-function experiments revealed that reduced Zdbf2 levels impair hypothalamic circuit activation responsible for stimulating appetite, leading to decreased Insulin Growth Factor 1 (IGF-1) levels, milk deprivation, and compromised neonatal growth and survival. These data underscore that the precise control of imprinted gene expression within the Gpr1-Zdbf2 domain is indispensable for the successful transition from intra- to extrauterine life."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "5"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Hisato Kobayashi, Kaori Yamada, Shinnosuke Morita, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Identification of the mouse paternally expressed imprinted gene Zdbf2 on chromosome 1 and its imprinted human homolog ZDBF2 on chromosome 2."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Genomics (2009)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.ygeno.2008.12.012"}], "href": "https://doi.org/10.1016/j.ygeno.2008.12.012"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19200453"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19200453"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Rachel Duffié, Sophie Ajjan, Maxim V Greenberg, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The Gpr1/Zdbf2 locus provides new paradigms for transient and dynamic genomic imprinting in mammals."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Genes Dev (2014)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1101/gad.232058.113"}], "href": "https://doi.org/10.1101/gad.232058.113"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "24589776"}], "href": "https://pubmed.ncbi.nlm.nih.gov/24589776"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Hitoshi Hiura, Atsushi Sugawara, Hidehiko Ogawa, et al. "}, {"type": "b", "children": [{"type": "t", "text": "A tripartite paternally methylated region within the Gpr1-Zdbf2 imprinted domain on mouse chromosome 1 identified by meDIP-on-chip."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nucleic Acids Res (2010)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1093/nar/gkq200"}], "href": "https://doi.org/10.1093/nar/gkq200"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "20385583"}], "href": "https://pubmed.ncbi.nlm.nih.gov/20385583"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Hisato Kobayashi, Takayuki Sakurai, Shun Sato, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Imprinted DNA methylation reprogramming during early mouse embryogenesis at the Gpr1-Zdbf2 locus is linked to long cis-intergenic transcription."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "FEBS Lett (2012)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.febslet.2012.01.059"}], "href": "https://doi.org/10.1016/j.febslet.2012.01.059"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "22449967"}], "href": "https://pubmed.ncbi.nlm.nih.gov/22449967"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Juliane Glaser, Julian Iranzo, Maud Borensztein, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The imprinted "}, {"type": "a", "children": [{"type": "t", "text": "i"}], "href": "i"}, {"type": "t", "text": "Zdbf2"}, {"type": "a", "children": [{"type": "t", "text": "/i"}], "href": "/i"}, {"type": "t", "text": " gene finely tunes control of feeding and growth in neonates."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Elife (2022)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.7554/eLife.65641"}], "href": "https://doi.org/10.7554/eLife.65641"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "35049495"}], "href": "https://pubmed.ncbi.nlm.nih.gov/35049495"}]}]}]}