Newly identified Gon4l/Udu-interacting proteins implicate novel functions

Abstract

Mutations of the Gon4l/udu gene in different organisms give rise to diverse phenotypes. Although the effects of Gon4l/Udu in transcriptional regulation have been demonstrated, they cannot solely explain the observed characteristics among species. To further understand the function of Gon4l/Udu, we used yeast two-hybrid (Y2H) screening to identify interacting proteins in zebrafish and mouse systems, confirmed the interactions by co-immunoprecipitation assay, and found four novel Gon4l-interacting proteins: BRCA1 associated protein-1 (Bap1), DNA methyltransferase 1 (Dnmt1), Tho complex 1 (Thoc1, also known as Tho1 or HPR1), and Cryptochrome circadian regulator 3a (Cry3a). Furthermore, all known Gon4l/Udu-interacting proteins-as found in this study, in previous reports, and in online resources-were investigated by Phenotype Enrichment Analysis. The most enriched phenotypes identified include increased embryonic tissue cell apoptosis, embryonic lethality, increased T cell derived lymphoma incidence, decreased cell proliferation, chromosome instability, and abnormal dopamine level, characteristics that largely resemble those observed in reported Gon4l/udu mutant animals. Similar to the expression pattern of udu, those of bap1, dnmt1, thoc1, and cry3a are also found in the brain region and other tissues. Thus, these findings indicate novel mechanisms of Gon4l/ Udu in regulating CpG methylation, histone expression/modification, DNA repair/genomic stability, and RNA binding/processing/export.

Zebrafish Cancer Predisposition Models

“…Further, in prim1 (DNA primase subunit 1) zebrafish mutants, knockdown of atm or atr is too toxic for retinal development, but retinal apoptosis due to DNA damage from faulty DNA replication is mostly suppressed with chemical inhibition of ATM (via KU55933) or ATM/ATR (via CGK733), or knockdown of chk2 (Yamaguchi et al, 2008). Similar observations were made in the ugly duckling (udu) zebrafish mutant now mapped to the gon4l gene which has been recently implicated in regulating several pleotropic mechanisms including DNA repair and genome stability (Lim et al, 2009;Tsai et al, 2020). p53-mediated apoptosis in this mutant could be successfully inhibited by either knockdown of tp53, chk2 or chemical inhibition of ATM.…”

Genome-Wide Gene Expression Profiles Reveal Distinct Molecular Characteristics of the Goose Granulosa Cells

“…The hub genes identified in cluster 1 were Gon4l , NUMA1, and SAFB1 ( Supplementary Figure S4A ). Gon4l was conserved within the animal species ( Tsai et al, 2020 ), with crucial roles in cell proliferation, cell differentiation, cell cycle, cell viability, embryonic patterning, cardiomyocyte proliferation, and ventricular fate maintenance in worms, flies, mice, and fish ( Friedman et al, 2000 ; Liu et al, 2007 ; Bulchand et al, 2010 ; Lu et al, 2010 ; Colgan et al, 2021 ). Moreover, Gon4l has been reported to participate in cell proliferation, cell survival, and mesoderm-derived tissue specification including those of the blood and somites in the zebrafish, ( Budine et al, 2020 ).…”