scholarly journals DNA Methylation Restricts Lineage-specific Functions of Transcription Factor Gata4 during Embryonic Stem Cell Differentiation

PLoS Genetics ◽  
2013 ◽  
Vol 9 (6) ◽  
pp. e1003574 ◽  
Author(s):  
Masaaki Oda ◽  
Yuichi Kumaki ◽  
Masaki Shigeta ◽  
Lars Martin Jakt ◽  
Chisa Matsuoka ◽  
...  
PLoS Genetics ◽  
2021 ◽  
Vol 17 (4) ◽  
pp. e1009498
Author(s):  
Adi Alajem ◽  
Hava Roth ◽  
Sofia Ratgauzer ◽  
Danny Bavli ◽  
Alex Motzik ◽  
...  

In mammals, cellular identity is defined through strict regulation of chromatin modifications and DNA methylation that control gene expression. Methylation of cytosines at CpG sites in the genome is mainly associated with suppression; however, the reason for enhancer-specific methylation is not fully understood. We used sequential ChIP-bisulfite-sequencing for H13K4me1 and H3K27ac histone marks. By collecting data from the same genomic region, we identified enhancers differentially methylated between these two marks. We observed a global gain of CpG methylation primarily in H3K4me1-marked nucleosomes during mouse embryonic stem cell differentiation. This gain occurred largely in enhancer regions that regulate genes critical for differentiation. The higher levels of DNA methylation in H3K4me1- versus H3K27ac-marked enhancers, despite it being the same genomic region, indicates cellular heterogeneity of enhancer states. Analysis of single-cell RNA-seq profiles demonstrated that this heterogeneity correlates with gene expression during differentiation. Furthermore, heterogeneity of enhancer methylation correlates with transcription start site methylation. Our results provide insights into enhancer-based functional variation in complex biological systems.


PLoS ONE ◽  
2011 ◽  
Vol 6 (10) ◽  
pp. e26052 ◽  
Author(s):  
Takayuki Isagawa ◽  
Genta Nagae ◽  
Nobuaki Shiraki ◽  
Takanori Fujita ◽  
Noriko Sato ◽  
...  

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