Cytoskeletal Protein Zyxin Inhibits the Activity of Genes Responsible for Embryonic Stem Cell Status
Autor: | Nadezhda Zhigalova, Fatima K. Gyoeva, Dmitry B. Staroverov, Eugeny E. Оrlov, Natalia Y. Martynova, Andrey G. Zaraisky, Arina G. Shokhina, Fedor M. Eroshkin, Elena A. Parshina, Vsevolod V. Belousov, Egor Prokhortchouk |
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Rok vydání: | 2020 |
Předmět: |
Homeobox protein NANOG
Cellular differentiation Biology Nanog General Biochemistry Genetics and Molecular Biology Zyxin Ybx1 Kruppel-Like Factor 4 Xenopus laevis actin cytoskeleton regulation Morphogenesis Animals Humans lcsh:QH301-705.5 Cytoskeleton Embryonic Stem Cells Zebrafish Body Patterning Neural Plate HEK 293 cells Gene Expression Regulation Developmental Cell Differentiation MRNA stabilization Actin cytoskeleton Embryonic stem cell genes responsible for stem cells status Cell biology Cytoskeletal Proteins HEK293 Cells lcsh:Biology (General) KLF4 embryonic structures Octamer Transcription Factor-3 pou5f3 |
Zdroj: | Cell Reports, Vol 33, Iss 7, Pp 108396-(2020) |
ISSN: | 1556-5068 |
DOI: | 10.2139/ssrn.3554017 |
Popis: | Summary: Zyxin is a cytoskeletal LIM-domain protein that regulates actin cytoskeleton assembly and gene expression. In the present work, we find that zyxin downregulation in Xenopus laevis embryos reduces the expression of numerous genes that regulate cell differentiation, but it enhances that of several genes responsible for embryonic stem cell status, specifically klf4, pou5f3.1, pou5f3.2, pou5f3.3, and vent2.1/2. For pou5f3 family genes (mammalian POU5F1/OCT4 homologs), we show that this effect is the result of mRNA stabilization due to complex formation with the Y-box protein Ybx1. When bound to Ybx1, zyxin interferes with the formation of these complexes, thereby stimulating pou5f3 mRNA degradation. In addition, in zebrafish embryos and human HEK293 cells, zyxin downregulation increases mRNA levels of the pluripotency genes KLF4, NANOG, and POU5F1/OCT4. Our findings indicate that zyxin may play a role as a switch among morphogenetic cell movement, differentiation, and embryonic stem cell status. |
Databáze: | OpenAIRE |
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