FMRI Epigenetic Silencing Commonly Occurs in Undifferentiated Fragile X-Affected Embryonic Stem Cells

作者：Avitzour Michal; Mor Shaked Hagar; Yanovsky Dagan Shira; Aharoni Shira; Altarescu Gheona; Renbaum Paul; Eldar Geva Talia; Schonberger Oshrat; Levy Lahad Ephrat; Epsztejn Litman Silvina; Eiges Rachel^*

来源：Stem Cell Reports, 2014, 3(5): 699-706.

DOI：10.1016/j.stemcr.2014.09.001

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 FMRI 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.

• 出版日期2014-11-11
• 单位河北医科大学