PAX7 Balances the Cell Cycle Progression via Regulating Expression of <i>Dnmt3b</i> and <i>Apobec2</i> in Differentiating PSCs
Anita Florkowska,
Igor Meszka,
Joanna Nowacka,
Monika Granica,
Zuzanna Jablonska,
Magdalena Zawada,
Lukasz Truszkowski,
Maria A. Ciemerych,
Iwona Grabowska
Affiliations
Anita Florkowska
Department of Cytology, Institute of Developmental Biology and Biomedical Sciences, Faculty of Biology, University of Warsaw, Miecznikowa 1, 02-096 Warsaw, Poland
Igor Meszka
Department of Cytology, Institute of Developmental Biology and Biomedical Sciences, Faculty of Biology, University of Warsaw, Miecznikowa 1, 02-096 Warsaw, Poland
Joanna Nowacka
Department of Cytology, Institute of Developmental Biology and Biomedical Sciences, Faculty of Biology, University of Warsaw, Miecznikowa 1, 02-096 Warsaw, Poland
Monika Granica
Department of Cytology, Institute of Developmental Biology and Biomedical Sciences, Faculty of Biology, University of Warsaw, Miecznikowa 1, 02-096 Warsaw, Poland
Zuzanna Jablonska
Department of Cytology, Institute of Developmental Biology and Biomedical Sciences, Faculty of Biology, University of Warsaw, Miecznikowa 1, 02-096 Warsaw, Poland
Magdalena Zawada
Department of Cytology, Institute of Developmental Biology and Biomedical Sciences, Faculty of Biology, University of Warsaw, Miecznikowa 1, 02-096 Warsaw, Poland
Lukasz Truszkowski
Department of Cytology, Institute of Developmental Biology and Biomedical Sciences, Faculty of Biology, University of Warsaw, Miecznikowa 1, 02-096 Warsaw, Poland
Maria A. Ciemerych
Department of Cytology, Institute of Developmental Biology and Biomedical Sciences, Faculty of Biology, University of Warsaw, Miecznikowa 1, 02-096 Warsaw, Poland
Iwona Grabowska
Department of Cytology, Institute of Developmental Biology and Biomedical Sciences, Faculty of Biology, University of Warsaw, Miecznikowa 1, 02-096 Warsaw, Poland
PAX7 transcription factor plays a crucial role in embryonic myogenesis and in adult muscles in which it secures proper function of satellite cells, including regulation of their self renewal. PAX7 downregulation is necessary for the myogenic differentiation of satellite cells induced after muscle damage, what is prerequisite step for regeneration. Using differentiating pluripotent stem cells we documented that the absence of functional PAX7 facilitates proliferation. Such action is executed by the modulation of the expression of two proteins involved in the DNA methylation, i.e., Dnmt3b and Apobec2. Increase in Dnmt3b expression led to the downregulation of the CDK inhibitors and facilitated cell cycle progression. Changes in Apobec2 expression, on the other hand, differently impacted proliferation/differentiation balance, depending on the experimental model used.
