Sumoylation regulates functional properties of the oocyte transcription factors SOHLH1 and NOBOX.

Autor: Patton BK; Department of Pathology & Immunology, Baylor College of Medicine, Houston, Texas, USA.; Graduate Program in Molecular & Cellular Biology, Baylor College of Medicine, Houston, Texas, USA., Madadi S; Department of Pathology & Immunology, Baylor College of Medicine, Houston, Texas, USA.; Rice University, Houston, Texas, USA., Briley SM; Department of Pathology & Immunology, Baylor College of Medicine, Houston, Texas, USA.; Graduate Program in Biochemistry & Molecular Biology, Baylor College of Medicine, Houston, Texas, USA., Ahmed AA; Department of Pathology & Immunology, Baylor College of Medicine, Houston, Texas, USA.; Graduate Program in Development, Disease Models & Therapeutics, Baylor College of Medicine, Houston, Texas, USA., Pangas SA; Department of Pathology & Immunology, Baylor College of Medicine, Houston, Texas, USA.; Graduate Program in Molecular & Cellular Biology, Baylor College of Medicine, Houston, Texas, USA.; Graduate Program in Biochemistry & Molecular Biology, Baylor College of Medicine, Houston, Texas, USA.; Graduate Program in Development, Disease Models & Therapeutics, Baylor College of Medicine, Houston, Texas, USA.; Department of Molecular & Cellular Biology, Baylor College of Medicine, Houston, Texas, USA.
Jazyk: angličtina
Zdroj: FASEB journal : official publication of the Federation of American Societies for Experimental Biology [FASEB J] 2023 Feb; Vol. 37 (2), pp. e22747.
DOI: 10.1096/fj.202201481R
Abstrakt: SOHLH1 and NOBOX are oocyte-expressed transcription factors with critical roles in ovary development and fertility. In mice, Sohlh1 and Nobox are essential for fertility through their regulation of the oocyte transcriptional network and cross-talk to somatic cells. Sumoylation is a posttranslational modification that regulates transcription factor function, and we previously showed that mouse oocytes deficient for sumoylation had an altered transcriptional landscape that included significant changes in NOBOX target genes. Here, we show that mouse SOHLH1 is modified by SUMO2/3 at lysine 345 and mutation of this residue alters SOHLH1 nuclear to cytoplasmic localization. In NOBOX, we identify a non-consensus SUMO site, K97, that eliminates NOBOX mono-SUMO2/3 conjugation, while a point mutation at K125 had no effect on NOBOX sumoylation. However, NOBOX K97R/K125R double mutants showed loss of mono-SUMO2/3 and altered higher molecular weight modifications, suggesting cooperation between these lysine's. NOBOX K97R and NOBOX K97R/K125R differentially regulated NOBOX promoter targets, with increased activity on the Gdf9 promoter, but no effect on the Pou5f1 promoter. These data implicate sumoylation as a novel regulatory mechanism for SOHLH1 and NOBOX, which may prove useful in refining their roles during oogenesis as well as their function during reprogramming to generate de novo germ cells.
(© 2023 Federation of American Societies for Experimental Biology.)
Databáze: MEDLINE
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