FMR1 Epigenetic Silencing Commonly Occurs in Undifferentiated Fragile X-Affected Embryonic Stem Cells
| العنوان: | FMR1 Epigenetic Silencing Commonly Occurs in Undifferentiated Fragile X-Affected Embryonic Stem Cells |
|---|---|
| المؤلفون: | Shira Yanovsky-Dagan, Talia Eldar-Geva, Ephrat Levy-Lahad, Shira Aharoni, Rachel Eiges, Michal Avitzour, Silvina Epsztejn-Litman, Gheona Altarescu, Paul Renbaum, Hagar Mor-Shaked, Oshrat Schonberger |
| المصدر: | Stem Cell Reports, Vol 3, Iss 5, Pp 699-706 (2014) Stem Cell Reports |
| بيانات النشر: | Elsevier, 2014. |
| سنة النشر: | 2014 |
| مصطلحات موضوعية: | congenital, hereditary, and neonatal diseases and abnormalities, Blotting, Western, Gene Expression, Biology, Biochemistry, Methylation, X-inactivation, Cell Line, Epigenesis, Genetic, Histones, Fragile X Mental Retardation Protein, X Chromosome Inactivation, Report, Genetics, medicine, Gene silencing, Humans, Epigenetics, Gene Silencing, lcsh:QH301-705.5, Embryonic Stem Cells, lcsh:R5-920, Reverse Transcriptase Polymerase Chain Reaction, Lysine, SOXB1 Transcription Factors, Cell Biology, Sequence Analysis, DNA, DNA Methylation, medicine.disease, Embryonic stem cell, FMR1, Fragile X syndrome, lcsh:Biology (General), Fragile X Syndrome, DNA methylation, Trinucleotide repeat expansion, 5' Untranslated Regions, Trinucleotide Repeat Expansion, lcsh:Medicine (General), Octamer Transcription Factor-3, Developmental Biology |
| الوصف: | Summary Fragile X syndrome (FXS) is the most common heritable form of cognitive impairment. It results from epigenetic silencing of the X-linked FMR1 gene by a CGG expansion in its 5′-untranslated region. Taking advantage of a large set of FXS-affected human embryonic stem cell (HESC) lines and isogenic subclones derived from them, we show that FMR1 hypermethylation commonly occurs in the undifferentiated state (six of nine lines, ranging from 24% to 65%). In addition, we demonstrate that hypermethylation is tightly linked with FMR1 transcriptional inactivation in undifferentiated cells, coincides with loss of H3K4me2 and gain of H3K9me3, and is unrelated to CTCF binding. Taken together, these results demonstrate that FMR1 epigenetic gene silencing takes place in FXS HESCs and clearly highlights the importance of examining multiple cell lines when investigating FXS and most likely other epigenetically regulated diseases. Highlights • FMR1 epigenetic gene silencing commonly occurs in the undifferentiated FXS cells • FXS HESCs are heterogeneous for repeat size and methylation levels • This study underscores the importance of multiple HESC lines in disease modeling Fragile X syndrome (FXS) results from epigenetic silencing of the X-linked FMR1 gene. Using a large set of fragile X-affected human embryonic stem cell lines, Eiges and colleagues show that FMR1 epigenetic gene inactivation commonly occurs prior to embryonic tissue differentiation. This study underscores the importance of examining multiple cell lines in disease modeling, especially in epigenetically regulated disorders like FXS. |
| اللغة: | English |
| تدمد: | 2213-6711 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::5acdf984a3609ad5be8e222fb797d19e http://www.sciencedirect.com/science/article/pii/S2213671114002860 |
| حقوق: | OPEN |
| رقم الأكسشن: | edsair.doi.dedup.....5acdf984a3609ad5be8e222fb797d19e |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 22136711 |
|---|