Epigenetic Characterization of the FMR1 Promoter in Induced Pluripotent Stem Cells from Human Fibroblasts Carrying an Unmethylated Full Mutation
Silencing of the FMR1 gene leads to fragile X syndrome, the most common cause of inherited intellectual disability. To study the epigenetic modifications of the FMR1 gene during silencing in time, we used fibroblasts and induced pluripotent stem cells (iPSCs) of an unmethylated full mutation (uFM) i...
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| Format: | Online |
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Elsevier
2014
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| Online Access: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4223701/ |
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pubmed-42237012014-11-09 Epigenetic Characterization of the FMR1 Promoter in Induced Pluripotent Stem Cells from Human Fibroblasts Carrying an Unmethylated Full Mutation de Esch, Celine E.F. Ghazvini, Mehrnaz Loos, Friedemann Schelling-Kazaryan, Nune Widagdo, W. Munshi, Shashini T. van der Wal, Erik Douben, Hannie Gunhanlar, Nilhan Kushner, Steven A. Pijnappel, W.W.M. Pim de Vrij, Femke M.S. Geijsen, Niels Gribnau, Joost Willemsen, Rob Report Silencing of the FMR1 gene leads to fragile X syndrome, the most common cause of inherited intellectual disability. To study the epigenetic modifications of the FMR1 gene during silencing in time, we used fibroblasts and induced pluripotent stem cells (iPSCs) of an unmethylated full mutation (uFM) individual with normal intelligence. The uFM fibroblast line carried an unmethylated FMR1 promoter region and expressed normal to slightly increased FMR1 mRNA levels. The FMR1 expression in the uFM line corresponds with the increased H3 acetylation and H3K4 methylation in combination with a reduced H3K9 methylation. After reprogramming, the FMR1 promoter region was methylated in all uFM iPSC clones. Two clones were analyzed further and showed a lack of FMR1 expression, whereas the presence of specific histone modifications also indicated a repressed FMR1 promoter. In conclusion, these findings demonstrate that the standard reprogramming procedure leads to epigenetic silencing of the fully mutated FMR1 gene. Elsevier 2014-09-11 /pmc/articles/PMC4223701/ /pubmed/25358783 http://dx.doi.org/10.1016/j.stemcr.2014.07.013 Text en © 2014 The Authors http://creativecommons.org/licenses/by-nc-nd/3.0/ This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/3.0/). |
| repository_type |
Open Access Journal |
| institution_category |
Foreign Institution |
| institution |
US National Center for Biotechnology Information |
| building |
NCBI PubMed |
| collection |
Online Access |
| language |
English |
| format |
Online |
| author |
de Esch, Celine E.F. Ghazvini, Mehrnaz Loos, Friedemann Schelling-Kazaryan, Nune Widagdo, W. Munshi, Shashini T. van der Wal, Erik Douben, Hannie Gunhanlar, Nilhan Kushner, Steven A. Pijnappel, W.W.M. Pim de Vrij, Femke M.S. Geijsen, Niels Gribnau, Joost Willemsen, Rob |
| spellingShingle |
de Esch, Celine E.F. Ghazvini, Mehrnaz Loos, Friedemann Schelling-Kazaryan, Nune Widagdo, W. Munshi, Shashini T. van der Wal, Erik Douben, Hannie Gunhanlar, Nilhan Kushner, Steven A. Pijnappel, W.W.M. Pim de Vrij, Femke M.S. Geijsen, Niels Gribnau, Joost Willemsen, Rob Epigenetic Characterization of the FMR1 Promoter in Induced Pluripotent Stem Cells from Human Fibroblasts Carrying an Unmethylated Full Mutation |
| author_facet |
de Esch, Celine E.F. Ghazvini, Mehrnaz Loos, Friedemann Schelling-Kazaryan, Nune Widagdo, W. Munshi, Shashini T. van der Wal, Erik Douben, Hannie Gunhanlar, Nilhan Kushner, Steven A. Pijnappel, W.W.M. Pim de Vrij, Femke M.S. Geijsen, Niels Gribnau, Joost Willemsen, Rob |
| author_sort |
de Esch, Celine E.F. |
| title |
Epigenetic Characterization of the FMR1 Promoter in Induced Pluripotent Stem Cells from Human Fibroblasts Carrying an Unmethylated Full Mutation |
| title_short |
Epigenetic Characterization of the FMR1 Promoter in Induced Pluripotent Stem Cells from Human Fibroblasts Carrying an Unmethylated Full Mutation |
| title_full |
Epigenetic Characterization of the FMR1 Promoter in Induced Pluripotent Stem Cells from Human Fibroblasts Carrying an Unmethylated Full Mutation |
| title_fullStr |
Epigenetic Characterization of the FMR1 Promoter in Induced Pluripotent Stem Cells from Human Fibroblasts Carrying an Unmethylated Full Mutation |
| title_full_unstemmed |
Epigenetic Characterization of the FMR1 Promoter in Induced Pluripotent Stem Cells from Human Fibroblasts Carrying an Unmethylated Full Mutation |
| title_sort |
epigenetic characterization of the fmr1 promoter in induced pluripotent stem cells from human fibroblasts carrying an unmethylated full mutation |
| description |
Silencing of the FMR1 gene leads to fragile X syndrome, the most common cause of inherited intellectual disability. To study the epigenetic modifications of the FMR1 gene during silencing in time, we used fibroblasts and induced pluripotent stem cells (iPSCs) of an unmethylated full mutation (uFM) individual with normal intelligence. The uFM fibroblast line carried an unmethylated FMR1 promoter region and expressed normal to slightly increased FMR1 mRNA levels. The FMR1 expression in the uFM line corresponds with the increased H3 acetylation and H3K4 methylation in combination with a reduced H3K9 methylation. After reprogramming, the FMR1 promoter region was methylated in all uFM iPSC clones. Two clones were analyzed further and showed a lack of FMR1 expression, whereas the presence of specific histone modifications also indicated a repressed FMR1 promoter. In conclusion, these findings demonstrate that the standard reprogramming procedure leads to epigenetic silencing of the fully mutated FMR1 gene. |
| publisher |
Elsevier |
| publishDate |
2014 |
| url |
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4223701/ |
| _version_ |
1613153552066150400 |