{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nZPBP2 is a testis‐specific gene that belongs to the zona pellucida binding protein family and plays an important structural role during spermiogenesis. Studies in mice have demonstrated that deletion or disruption of ZPBP2 results in abnormal acrosome compaction and dysmorphic spermatozoa, underlining its critical contribution to proper sperm development. Consistent with these findings, clinical investigations in non‐obstructive azoospermia patients revealed that higher ZPBP2 expression levels are associated with a greater fraction of haploid cells and improved outcomes during sperm retrieval procedures."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nWithin the chromosome 17q12–q21 locus—which is linked to several immune‐mediated diseases including asthma—ZPBP2 is part of a cluster whose expression is regulated in an allele‐specific manner. Detailed functional studies have uncovered that single nucleotide polymorphisms can modulate the activity of the ZPBP2 promoter by affecting local nucleosome positioning and transcription factor binding. Furthermore, variable levels of DNA methylation at the gene’s regulatory regions can either mask or enhance these genetic effects, underscoring a complex interplay between genetic variants and epigenetic modifications in controlling ZPBP2 transcription in immune‐related contexts."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "3"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nAdding another layer to its multifaceted regulation, recent evidence indicates that the expression of ZPBP2 is subject to circadian rhythms in both human and mouse tissues. Diurnal variations in ZPBP2 transcript levels have been observed, and the genomic region encompassing ZPBP2 has been shown to influence the expression profile of nearby core clock genes in a time‐dependent manner. This finding suggests that ZPBP2 not only plays a pivotal role in spermiogenesis and immunogenetics but also participates in the broader network of circadian regulation, potentially linking environmental cues with genetic and epigenetic control mechanisms."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "5"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Yi-Nan Lin, Angshumoy Roy, Wei Yan, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Loss of zona pellucida binding proteins in the acrosomal matrix disrupts acrosome biogenesis and sperm morphogenesis."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Cell Biol (2007)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1128/MCB.01029-07"}], "href": "https://doi.org/10.1128/MCB.01029-07"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "17664285"}], "href": "https://pubmed.ncbi.nlm.nih.gov/17664285"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Nasrin Ghanami Gashti, Mohammad Ali Sadighi Gilani, Ayob Jabari, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The Germ Cell-Specific Markers ZPBP2 and PGK2 in Testicular Biopsies Can Predict the Presence as well as the Quality of Sperm in Non-obstructive Azoospermia Patients."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Reprod Sci (2021)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1007/s43032-020-00427-9"}], "href": "https://doi.org/10.1007/s43032-020-00427-9"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "33507524"}], "href": "https://pubmed.ncbi.nlm.nih.gov/33507524"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Soizik Berlivet, Sanny Moussette, Manon Ouimet, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Interaction between genetic and epigenetic variation defines gene expression patterns at the asthma-associated locus 17q12-q21 in lymphoblastoid cell lines."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Hum Genet (2012)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1007/s00439-012-1142-x"}], "href": "https://doi.org/10.1007/s00439-012-1142-x"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "22271045"}], "href": "https://pubmed.ncbi.nlm.nih.gov/22271045"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Sanny Moussette, Abeer Al Tuwaijri, Hamid-Reza Kohan-Ghadr, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Role of DNA methylation in expression control of the IKZF3-GSDMA region in human epithelial cells."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "PLoS One (2017)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1371/journal.pone.0172707"}], "href": "https://doi.org/10.1371/journal.pone.0172707"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "28241063"}], "href": "https://pubmed.ncbi.nlm.nih.gov/28241063"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Matthew L Chang, Sanny Moussette, Enrique Gamero-Estevez, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Regulatory interaction between the ZPBP2-ORMDL3/Zpbp2-Ormdl3 region and the circadian clock."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "PLoS One (2019)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1371/journal.pone.0223212"}], "href": "https://doi.org/10.1371/journal.pone.0223212"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "31560728"}], "href": "https://pubmed.ncbi.nlm.nih.gov/31560728"}]}]}]}