Epigenetic Characterization of the FMR1 Promoter in Induced Pluripotent Stem Cells from Human Fibroblasts Carrying an Unmethylated Full Mutation

被引:44
|
作者
de Esch, Celine E. F. [1 ]
Ghazvini, Mehrnaz [2 ,3 ]
Loos, Friedemann [3 ]
Schelling-Kazaryan, Nune [4 ,5 ]
Widagdo, W. [1 ]
Munshi, Shashini T. [6 ]
van der Wal, Erik [7 ,8 ]
Douben, Hannie [1 ]
Gunhanlar, Nilhan [6 ]
Kushner, Steven A. [6 ]
Pijnappel, W. W. M. Pim [7 ,8 ]
de Vrij, Femke M. S. [6 ]
Geijsen, Niels [4 ,5 ,9 ]
Gribnau, Joost [3 ]
Willemsen, Rob [1 ]
机构
[1] Erasmus MC, Dept Clin Genet, NL-3015 GE Rotterdam, Netherlands
[2] Erasmus MC, iPS Cell Facil, NL-3015 GE Rotterdam, Netherlands
[3] Erasmus MC, Dept Reprod & Dev, NL-3015 GE Rotterdam, Netherlands
[4] KNAW Hubrecht Inst, NL-3584 CT Utrecht, Netherlands
[5] UMC Utrecht, NL-3584 CT Utrecht, Netherlands
[6] Erasmus MC, Dept Psychiat, NL-3015 GE Rotterdam, Netherlands
[7] Erasmus MC, Ctr Lysosomal & Metab Dis, Dept Clin Genet, NL-3015 GE Rotterdam, Netherlands
[8] Erasmus MC, Ctr Lysosomal & Metab Dis, Dept Pediat, Div Metab Dis & Genet, NL-3015 GE Rotterdam, Netherlands
[9] Univ Utrecht, Sch Vet Med, Dept Compan Anim, NL-3508 TD Utrecht, Netherlands
来源
STEM CELL REPORTS | 2014年 / 3卷 / 04期
关键词
FRAGILE-X-SYNDROME; GENE; REACTIVATION;
D O I
10.1016/j.stemcr.2014.07.013
中图分类号
Q813 [细胞工程];
学科分类号
摘要
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.
引用
收藏
页码:548 / 555
页数:8
相关论文
共 50 条
  • [21] Fragile X males with unmethylated, full mutation trinucleotide repeat expansions have elevated levels of FMR1 messenger RNA
    Tassone, F
    Hagerman, RJ
    Loesch, DZ
    Lachiewicz, A
    Taylor, AK
    Hagerman, PJ
    AMERICAN JOURNAL OF MEDICAL GENETICS, 2000, 94 (03): : 232 - 236
  • [22] Generation and characterization of induced pluripotent stem cells from a family carrying the BRCA1 mutation c.3612delA
    Silva, Teresa P.
    Pereira, Carolina A.
    Oliveira, Ana Rita
    Raposo, Ana Claudia
    Arez, Maria
    Cabral, Joaquim M. S.
    Milagre, Ines
    Carmo-Fonseca, Maria
    da Rocha, Simao T.
    STEM CELL RESEARCH, 2021, 52
  • [23] Generation and characterization of functional cardiomyocytes using induced pluripotent stem cells derived from human fibroblasts
    Gai, Hui
    Leung, Elaine Lai-Han
    Costantino, Peter D.
    Aguila, Jerell R.
    Nguyen, David M.
    Fink, Louis M.
    Ward, David C.
    Ma, Yupo
    CELL BIOLOGY INTERNATIONAL, 2009, 33 (11) : 1184 - 1193
  • [24] Induced Pluripotent Stem Cells From Goat Fibroblasts
    Song, Hui
    Li, Hui
    Huang, Mingrui
    Xu, Dan
    Gu, Chenghao
    Wang, Ziyu
    Dong, Fulu
    Wang, Feng
    MOLECULAR REPRODUCTION AND DEVELOPMENT, 2013, 80 (12) : 1009 - 1017
  • [25] Enhanced Generation of Induced Pluripotent Stem Cells from a Subpopulation of Human Fibroblasts
    Byrne, James A.
    Nguyen, Ha Nam
    Pera, Renee A. Reijo
    PLOS ONE, 2009, 4 (09):
  • [26] Generation of induced pluripotent stem cells (iPSCs) from human foreskin fibroblasts
    Erdlenbruch, Friedrich
    Rohwedel, Juergen
    Ralfs, Philipp
    Thomitzek, Antonia
    Kramer, Jan
    Cakiroglu, Figen
    STEM CELL RESEARCH, 2018, 33 : 79 - 82
  • [27] Derivation of Induced Pluripotent Stem Cells from Fetal Human Skin Fibroblasts
    Medvedev, S. P.
    Malakhova, A. A.
    Grigor'eva, E. V.
    Shevchenko, A. I.
    Dementyeva, E. V.
    Sobolev, I. A.
    Lebedev, I. N.
    Shilov, A. G.
    Zhimulev, I. F.
    Zakian, S. M.
    ACTA NATURAE, 2010, 2 (02): : 102 - 104
  • [28] Characterization of human-induced pluripotent stem cells carrying homozygous RB1 gene deletion
    Deng, Xiaoyue
    Iwagawa, Toshiro
    Fukushima, Masaya
    Watanabe, Sumiko
    GENES TO CELLS, 2020, 25 (07) : 510 - 517
  • [29] Differentiation of human induced pluripotent stem cells into dermal fibroblasts
    Itoh, M.
    Christiano, A. M.
    JOURNAL OF INVESTIGATIVE DERMATOLOGY, 2012, 132 : S140 - S140
  • [30] Generation of a human induced pluripotent stem cell line (FSMi001-A) from fibroblasts of a patient carrying heterozygous mutation in the REEP1 gene
    Baggiani, Matteo
    Santorelli, Filippo Maria
    Mero, Serena
    Privitera, Flavia
    Damiani, Devid
    Tessa, Alessandra
    STEM CELL RESEARCH, 2024, 79