scholarly journals Loss of DNA methyltransferase activity in primed human ES cells triggers increased cell-cell variability and transcriptional repression

Development ◽  
2019 ◽  
Vol 146 (19) ◽  
pp. dev174722 ◽  
Author(s):  
Alexander M. Tsankov ◽  
Marc H. Wadsworth ◽  
Veronika Akopian ◽  
Jocelyn Charlton ◽  
Samuel J. Allon ◽  
...  



2014 ◽  
Vol 12 (3) ◽  
pp. 630-637 ◽  
Author(s):  
Amita Tiyaboonchai ◽  
Helen Mac ◽  
Razveen Shamsedeen ◽  
Jason A. Mills ◽  
Siddarth Kishore ◽  
...  


2005 ◽  
Vol 25 (12) ◽  
pp. 4881-4891 ◽  
Author(s):  
Diana L. Carlone ◽  
Jeong-Heon Lee ◽  
Suzanne R. L. Young ◽  
Erika Dobrota ◽  
Jill Sergesketter Butler ◽  
...  

ABSTRACT Cytosine methylation at CpG dinucleotides is a critical epigenetic modification of mammalian genomes. CpG binding protein (CGBP) exhibits a unique DNA-binding specificity for unmethylated CpG motifs and is essential for early murine development. Embryonic stem cell lines deficient for CGBP were generated to further examine CGBP function. CGBP − / − cells are viable but show an increased rate of apoptosis and are unable to achieve in vitro differentiation following removal of leukemia inhibitory factor from the growth media. Instead, CGBP − / − embryonic stem cells remain undifferentiated as revealed by persistent expression of the pluripotent markers Oct4 and alkaline phosphatase. CGBP − / − cells exhibit a 60 to 80% decrease in global cytosine methylation, including hypo-methylation of repetitive elements, single-copy genes, and imprinted genes. Total DNA methyltransferase activity is reduced by 30 to 60% in CGBP − / − cells, and expression of the maintenance DNA methyltransferase 1 protein is similarly reduced. However, de novo DNA methyltransferase activity is normal. Nearly all aspects of the pleiotropic CGBP − / − phenotype are rescued by introduction of a CGBP expression vector. Hence, CGBP is essential for normal epigenetic modification of the genome by cytosine methylation and for cellular differentiation, consistent with the requirement for CGBP during early mammalian development.



FEBS Letters ◽  
1995 ◽  
Vol 361 (1) ◽  
pp. 115-117 ◽  
Author(s):  
Luisa Tosi ◽  
Francesco Aniello ◽  
Giuseppe Geraci ◽  
Margherita Branno


2018 ◽  
Vol 50 (3) ◽  
pp. 452-459 ◽  
Author(s):  
Silvana Rošić ◽  
Rachel Amouroux ◽  
Cristina E. Requena ◽  
Ana Gomes ◽  
Max Emperle ◽  
...  


1996 ◽  
Vol 93 (9) ◽  
pp. 4045-4050 ◽  
Author(s):  
S. A. Belinsky ◽  
K. J. Nikula ◽  
S. B. Baylin ◽  
J. P. Issa


2016 ◽  
Vol 59 (7) ◽  
pp. 809-815 ◽  
Author(s):  
Daiqi Li ◽  
Guoyan Lu ◽  
Chunyang Lei ◽  
Zhen Wang ◽  
Lijun Li ◽  
...  




2021 ◽  
Author(s):  
Masaki Shirai ◽  
Takuya Nara ◽  
Haruko Takahashi ◽  
Kazuya Takayama ◽  
Yuan Chen ◽  
...  

CpG methylation in genomic DNA is well known as a repressive epigenetic marker in eukaryotic transcription, and DNA methylation of the promoter regions is correlated with silencing of gene expression. In contrast to the promoter regions, the function of DNA methylation during transcription termination remains to be elucidated. A recent study has revealed that mouse DNA methyltransferase 3a (Dnmt3a) mainly functions in de novo methylation in the promoter and gene body regions (including transcription termination sites (TTSs)) during development. To investigate the relationship between DNA methylation overlapping the TTSs and transcription termination, we employed two strategies: informatic analysis using already deposited datasets of Dnmt3a-/- mouse cells and the zebrafish model system. Bioinformatic analysis using methylome and transcriptome data showed that hypomethylated differentially methylated regions overlapping the TTSs were associated with increased read counts and chimeric transcripts downstream of TTSs in Dnmt3a-/- Agouti-related protein neurons, but not in Dnmt3a-/- ES cells and MEFs. We experimentally detected increased read-through and chimeric transcripts downstream of hypomethylated TTSs in zebrafish maternal-zygotic dnmt3aa-/- mutants. This study is the first to identify transcription termination defects in DNA hypomethylated TTSs in Dnmt3a-/- vertebrates.



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