Covisualization of Global DNA Methylation/Hydroxymethylation and Protein Biomarkers for Ultrahigh-Definition Epigenetic Phenotyping of Stem Cells

Author(s):  
Jian Tajbakhsh
2014 ◽  
Vol 139 (1) ◽  
pp. 142-161 ◽  
Author(s):  
Marie-Claude Senut ◽  
Arko Sen ◽  
Pablo Cingolani ◽  
Asra Shaik ◽  
Susan J. Land ◽  
...  

2018 ◽  
Author(s):  
Juan Song ◽  
Adrian Janiszewski ◽  
Natalie De Geest ◽  
Lotte Vanheer ◽  
Irene Talon ◽  
...  

ABSTRACTDuring early mammalian development, the two X-chromosomes in female cells are active. Dosage compensation between XX female and XY male cells is then achieved by X-chromosome inactivation in female cells. Reprogramming female mouse somatic cells into induced pluripotent stem cells (iPSCs) leads to X-chromosome reactivation. The extent to which increased X-chromosome dosage (X-dosage) in female iPSCs leads to differences in the molecular and cellular properties of XX and XY iPSCs is still unclear. We show that chromatin accessibility in mouse iPSCs is modulated by X-dosage. Specific sets of transcriptional regulator motifs are enriched in chromatin with increased accessibility in XX or XY iPSCs. We show that the transcriptome, growth and pluripotency exit are also modulated by X-dosage in iPSCs. To understand the mechanisms by which increased X-dosage modulates the molecular and cellular properties of mouse pluripotent stem cells, we used heterozygous deletions of the X-linked gene Dusp9 in XX embryonic stem cells. We show that X-dosage regulates the transcriptome, open chromatin landscape, growth and pluripotency exit largely independently of global DNA methylation. Our results uncover new insights into X-dosage in pluripotent stem cells, providing principles of how gene dosage modulates the epigenetic and genetic mechanisms regulating cell identity.


2019 ◽  
Vol 12 (2) ◽  
pp. 333-350 ◽  
Author(s):  
Juan Song ◽  
Adrian Janiszewski ◽  
Natalie De Geest ◽  
Lotte Vanheer ◽  
Irene Talon ◽  
...  

2014 ◽  
Author(s):  
Eun Joon Lee ◽  
Prakash Rath ◽  
Jimei Liu ◽  
Dungsheng Ryu ◽  
Alan Free ◽  
...  

2020 ◽  
Vol 117 (31) ◽  
pp. 18439-18447
Author(s):  
Wendan Ren ◽  
Huitao Fan ◽  
Sara A. Grimm ◽  
Yiran Guo ◽  
Jae Jin Kim ◽  
...  

In mammals, repressive histone modifications such as trimethylation of histone H3 Lys9 (H3K9me3), frequently coexist with DNA methylation, producing a more stable and silenced chromatin state. However, it remains elusive how these epigenetic modifications crosstalk. Here, through structural and biochemical characterizations, we identified the replication foci targeting sequence (RFTS) domain of maintenance DNA methyltransferase DNMT1, a module known to bind the ubiquitylated H3 (H3Ub), as a specific reader for H3K9me3/H3Ub, with the recognition mode distinct from the typical trimethyl-lysine reader. Disruption of the interaction between RFTS and the H3K9me3Ub affects the localization of DNMT1 in stem cells and profoundly impairs the global DNA methylation and genomic stability. Together, this study reveals a previously unappreciated pathway through which H3K9me3 directly reinforces DNMT1-mediated maintenance DNA methylation.


2015 ◽  
Vol 42 (7) ◽  
pp. 355-371 ◽  
Author(s):  
Eun-Joon Lee ◽  
Prakash Rath ◽  
Jimei Liu ◽  
Dungsung Ryu ◽  
Lirong Pei ◽  
...  

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