biostudies-literatureKent BNIDDK NIH HHSNHLBI NIH HHSNCI NIH HHSNIHEllison Medical Foundation99-113https://www.ebi.ac.uk/biostudies/studies/S-EPMC4814311biostudies-literatureUnknown412(1)Landmark epigenetic events underlie early embryonic development, yet how epigenetic modifiers are regulated to achieve rapid epigenome re-patterning is not known. Uhrf1 and DNA methyltransferase 1 (Dnmt1) are known to largely mediate maintenance DNA methylation and Uhrf1 is also required for both Dnmt1 localization and stability. Here, we investigate how these two key epigenetic modifiers regulate early zebrafish development and characterize the developmental consequences of disrupting their homeostatic relationship. Unlike Uhrf1 knockdown, which causes developmental arrest and death prior to gastrulation, overexpression of human UHRF1 (WT-UHRF1) caused asymmetric epiboly, inefficient gastrulation and multi-systemic defects. UHRF1 phosphorylation was previously demonstrated as essential foDevelopmental biologyUHRF1 regulation of Dnmt1 is required for pre-gastrula zebrafish development.PMC4814311K23 HL103976R01 CA1548095R01CA154809R01 DK0807895R01HL1039765R01DK080789AG-SS-2482-10Walsh MJSadler KCKent BMagnani EfalseUHRF1 regulation of Dnmt1 is required for pre-gastrula zebrafish development.Landmark epigenetic events underlie early embryonic development, yet how epigenetic modifiers are regulated to achieve rapid epigenome re-patterning is not known. Uhrf1 and DNA methyltransferase 1 (Dnmt1) are known to largely mediate maintenance DNA methylation and Uhrf1 is also required for both Dnmt1 localization and stability. Here, we investigate how these two key epigenetic modifiers regulate early zebrafish development and characterize the developmental consequences of disrupting their homeostatic relationship. Unlike Uhrf1 knockdown, which causes developmental arrest and death prior to gastrulation, overexpression of human UHRF1 (WT-UHRF1) caused asymmetric epiboly, inefficient gastrulation and multi-systemic defects. UHRF1 phosphorylation was previously demonstrated as essential fo2016-01-01T00:00:00Z2016 Apr2025-04-21T18:35:06.545Z2019-03-27T03:10:42ZS-EPMC48143112685121410.1016/j.ydbio.2016.01.036