Utx is required for proper induction of ectoderm and mesoderm during differentiation of embryonic stem cells

Embryonic development requires chromatin remodeling for dynamic regulation of gene expression patterns to ensure silencing of pluripotent transcription factors and activation of developmental regulators. Demethylation of H3K27me3 by the histone demethylases Utx and Jmjd3 is important for the activat...

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Bibliographic Details
Published in:PloS one 2013-04, Vol.8 (4), p.e60020
Main Authors: Morales Torres, Cristina, Laugesen, Anne, Helin, Kristian
Format: Article
Language:English
Subjects:
Animals
Biology
Catalysis
Catalytic activity
Cell Differentiation
Cell Proliferation
Cells, Cultured
Chromatin remodeling
Demethylation
Differentiation
Ectoderm
Ectoderm - cytology
Embryo cells
Embryogenesis
Embryonic Development - genetics
Embryonic growth stage
Embryonic stem cells
Embryonic Stem Cells - physiology
Epigenetics
Gene expression
Gene Expression Regulation, Developmental
Gene Knockdown Techniques
Gene Knockout Techniques
Gene silencing
Genetic aspects
Genomics
Histone Demethylases - metabolism
Homology
Jumonji Domain-Containing Histone Demethylases - genetics
Jumonji Domain-Containing Histone Demethylases - metabolism
Male
Mesoderm
Mesoderm - cytology
Mice
Mice, 129 Strain
Minor Histocompatibility Antigens
Physiological aspects
Pluripotency
Promoter Regions, Genetic
Protein Binding
Proteins
Proteins - genetics
Proteins - metabolism
Regulators
Rodents
Stem cells
Transcription activation
Transcription factors
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Summary:Embryonic development requires chromatin remodeling for dynamic regulation of gene expression patterns to ensure silencing of pluripotent transcription factors and activation of developmental regulators. Demethylation of H3K27me3 by the histone demethylases Utx and Jmjd3 is important for the activation of lineage choice genes in response to developmental signals. To further understand the function of Utx in pluripotency and differentiation we generated Utx knockout embryonic stem cells (ESCs). Here we show that Utx is not required for the proliferation of ESCs, however, Utx contributes to the establishment of ectoderm and mesoderm in vitro. Interestingly, this contribution is independent of the catalytic activity of Utx. Furthermore, we provide data showing that the Utx homologue, Uty, which is devoid of detectable demethylase activity, and Jmjd3 partly compensate for the loss of Utx. Taken together our results show that Utx is required for proper formation of ectoderm and mesoderm in vitro, and that Utx, similar to its C.elegans homologue, has demethylase dependent and independent functions.
ISSN:1932-6203
1932-6203
DOI:10.1371/journal.pone.0060020