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Selective de-repression of germ cell-specific genes in mouse embryonic fibroblasts in a permissive epigenetic environment

Epigenetic modifications play crucial roles on establishment of tissue-specific transcription profiles and cellular characteristics. Direct conversions of fibroblasts into differentiated tissue cells by over-expression of critical transcription factors have been reported, but the epigenetic mechanis...

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Autores principales: Sekinaka, Tamotsu, Hayashi, Yohei, Noce, Toshiaki, Niwa, Hitoshi, Matsui, Yasuhisa
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5016969/
https://www.ncbi.nlm.nih.gov/pubmed/27608931
http://dx.doi.org/10.1038/srep32932
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author Sekinaka, Tamotsu
Hayashi, Yohei
Noce, Toshiaki
Niwa, Hitoshi
Matsui, Yasuhisa
author_facet Sekinaka, Tamotsu
Hayashi, Yohei
Noce, Toshiaki
Niwa, Hitoshi
Matsui, Yasuhisa
author_sort Sekinaka, Tamotsu
collection PubMed
description Epigenetic modifications play crucial roles on establishment of tissue-specific transcription profiles and cellular characteristics. Direct conversions of fibroblasts into differentiated tissue cells by over-expression of critical transcription factors have been reported, but the epigenetic mechanisms underlying these conversions are still not fully understood. In addition, conversion of somatic cells into germ cells has not yet been achieved. To understand epigenetic mechanisms that underlie germ cell characteristics, we attempted to use defined epigenetic factors to directly convert mouse embryonic fibroblasts (MEFs) into germ cells. Here, we successfully induced germ cell-specific genes by inhibiting repressive epigenetic modifications via RNAi or small-molecule compounds. Under these conditions, some tissue-specific genes and stimulus-inducible genes were also induced. Meanwhile, the treatments did not result in genome-wide transcriptional activation. These results suggested that a permissive epigenetic environment resulted in selective de-repression of stimulus- and differentiation-inducible genes including germ cell-specific genes in MEFs.
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spelling pubmed-50169692016-09-12 Selective de-repression of germ cell-specific genes in mouse embryonic fibroblasts in a permissive epigenetic environment Sekinaka, Tamotsu Hayashi, Yohei Noce, Toshiaki Niwa, Hitoshi Matsui, Yasuhisa Sci Rep Article Epigenetic modifications play crucial roles on establishment of tissue-specific transcription profiles and cellular characteristics. Direct conversions of fibroblasts into differentiated tissue cells by over-expression of critical transcription factors have been reported, but the epigenetic mechanisms underlying these conversions are still not fully understood. In addition, conversion of somatic cells into germ cells has not yet been achieved. To understand epigenetic mechanisms that underlie germ cell characteristics, we attempted to use defined epigenetic factors to directly convert mouse embryonic fibroblasts (MEFs) into germ cells. Here, we successfully induced germ cell-specific genes by inhibiting repressive epigenetic modifications via RNAi or small-molecule compounds. Under these conditions, some tissue-specific genes and stimulus-inducible genes were also induced. Meanwhile, the treatments did not result in genome-wide transcriptional activation. These results suggested that a permissive epigenetic environment resulted in selective de-repression of stimulus- and differentiation-inducible genes including germ cell-specific genes in MEFs. Nature Publishing Group 2016-09-09 /pmc/articles/PMC5016969/ /pubmed/27608931 http://dx.doi.org/10.1038/srep32932 Text en Copyright © 2016, The Author(s) http://creativecommons.org/licenses/by/4.0/ This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/
spellingShingle Article
Sekinaka, Tamotsu
Hayashi, Yohei
Noce, Toshiaki
Niwa, Hitoshi
Matsui, Yasuhisa
Selective de-repression of germ cell-specific genes in mouse embryonic fibroblasts in a permissive epigenetic environment
title Selective de-repression of germ cell-specific genes in mouse embryonic fibroblasts in a permissive epigenetic environment
title_full Selective de-repression of germ cell-specific genes in mouse embryonic fibroblasts in a permissive epigenetic environment
title_fullStr Selective de-repression of germ cell-specific genes in mouse embryonic fibroblasts in a permissive epigenetic environment
title_full_unstemmed Selective de-repression of germ cell-specific genes in mouse embryonic fibroblasts in a permissive epigenetic environment
title_short Selective de-repression of germ cell-specific genes in mouse embryonic fibroblasts in a permissive epigenetic environment
title_sort selective de-repression of germ cell-specific genes in mouse embryonic fibroblasts in a permissive epigenetic environment
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5016969/
https://www.ncbi.nlm.nih.gov/pubmed/27608931
http://dx.doi.org/10.1038/srep32932
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