scholarly journals Silencing of transposable elements may not be a major driver of regulatory evolution in primate induced pluripotent stem cells

2017 ◽  
Author(s):  
Michelle C. Ward ◽  
Siming Zhao ◽  
Kaixuan Luo ◽  
Bryan J. Pavlovic ◽  
Mohammad M. Karimi ◽  
...  

AbstractTransposable elements (TEs) comprise a substantial proportion of primate genomes. The regulatory potential of TEs can result in deleterious effects, especially during development. It has been suggested that, in pluripotent stem cells, TEs are targeted for silencing by KRAB-ZNF proteins, which recruit the TRIM28-SETDB1 complex, to deposit the repressive histone modification H3K9me3. TEs, in turn, can acquire mutations that allow them to evade detection by the host, and hence KRAB-ZNF proteins need to rapidly evolve to counteract them. To investigate the short-term evolution of TE silencing, we profiled the genome-wide distribution of H3K9me3 in induced pluripotent stem cells from ten human and seven chimpanzee individuals. We performed chromatin immunoprecipitation followed by high-throughput sequencing (ChIP-seq) for H3K9me3, as well as total RNA sequencing. We focused specifically on cross-species H3K9me3 ChIP-seq data that mapped to four million orthologous TEs. We found that, depending on the TE class, 10-60% of elements are marked by H3K9me3, with SVA, LTR and LINE elements marked most frequently. We found little evidence of inter-species differences in TE silencing, with as many as 80% of orthologous, putatively silenced, TEs marked at similar levels in humans and chimpanzees. Our data suggest limited species-specificity of TE silencing across six million years of primate evolution. Interestingly, the minority of TEs enriched for H3K9me3 in one species are not more likely to be associated with gene expression divergence of nearby orthologous genes. We conclude that orthologous TEs may not play a major role in driving gene regulatory divergence between humans and chimpanzees.

eLife ◽  
2018 ◽  
Vol 7 ◽  
Author(s):  
Michelle C Ward ◽  
Siming Zhao ◽  
Kaixuan Luo ◽  
Bryan J Pavlovic ◽  
Mohammad M Karimi ◽  
...  

Transposable elements (TEs) comprise almost half of primate genomes and their aberrant regulation can result in deleterious effects. In pluripotent stem cells, rapidly evolving KRAB-ZNF genes target TEs for silencing by H3K9me3. To investigate the evolution of TE silencing, we performed H3K9me3 ChIP-seq experiments in induced pluripotent stem cells from 10 human and 7 chimpanzee individuals. We identified four million orthologous TEs and found the SVA and ERV families to be marked most frequently by H3K9me3. We found little evidence of inter-species differences in TE silencing, with as many as 82% of putatively silenced TEs marked at similar levels in humans and chimpanzees. TEs that are preferentially silenced in one species are a similar age to those silenced in both species and are not more likely to be associated with expression divergence of nearby orthologous genes. Our data suggest limited species-specificity of TE silencing across 6 million years of primate evolution.


2014 ◽  
Vol 23 (4) ◽  
pp. 406-420 ◽  
Author(s):  
Olga Momčilović ◽  
Qiuyue Liu ◽  
Andrzej Swistowski ◽  
Tatiane Russo-Tait ◽  
Yiqiang Zhao ◽  
...  

2018 ◽  
Vol 11 ◽  
pp. 251686571880293 ◽  
Author(s):  
Adrian Janiszewski ◽  
Juan Song ◽  
Lotte Vanheer ◽  
Natalie De Geest ◽  
Vincent Pasque

How the epigenome of one cell type is remodeled during reprogramming into another unrelated type of cell remains unclear. Overexpression of transcription factors in somatic cells enables the induction of induced pluripotent stem cells (iPSCs). This process entails genome-wide remodeling of DNA methylation, chromatin, and transcription. Recent work suggests that the number of active X chromosomes present in a cell influences remodeling of DNA methylation during somatic cell reprogramming to mouse iPSCs. Female iPSCs with 2 active X chromosomes display global DNA hypomethylation, whereas male XY iPSCs show DNA methylation levels similar to the somatic cells they are derived from. Global DNA methylation erasure in female iPSCs takes place genome-wide and involves repression of DNA methyltransferases. However, on loss of one X chromosome, female iPSCs acquire a DNA methylation landscape resembling that of XY iPSCs. Therefore, it is the X chromosome dosage that dictates global DNA methylation levels in iPSCs. Here, we discuss the evidence that links X chromosome dosage with the regulation of DNA methylation in pluripotent stem cells. We focus on iPSCs reprogramming studies, where X chromosome status is a novel factor impacting our understanding of epigenetic remodeling.


Cell Research ◽  
2013 ◽  
Vol 24 (3) ◽  
pp. 293-306 ◽  
Author(s):  
Gang Chang ◽  
Shuai Gao ◽  
Xinfeng Hou ◽  
Zijian Xu ◽  
Yanfeng Liu ◽  
...  

2010 ◽  
Vol 34 (8) ◽  
pp. S36-S36
Author(s):  
Ping Duan ◽  
Xuelin Ren ◽  
Wenhai Yan ◽  
Xuefei Han ◽  
Xu Yan ◽  
...  

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