scholarly journals Decision letter: Functional evaluation of transposable elements as enhancers in mouse embryonic and trophoblast stem cells

2019 ◽  
Author(s):  
Deborah Bourc'his ◽  
Alvaro Rada-Iglesias ◽  
Dixie Mager
Keyword(s):  
Stem Cells ◽  
Transposable Elements ◽  
Functional Evaluation ◽  
Trophoblast Stem Cells ◽  
Trophoblast Stem

scholarly journals Functional evaluation of transposable elements as enhancers in mouse embryonic and trophoblast stem cells

eLife ◽  
2019 ◽  
Vol 8 ◽  
Author(s):  
Christopher D Todd ◽  
Özgen Deniz ◽  
Darren Taylor ◽  
Miguel R Branco
Keyword(s):  
Stem Cells ◽  
Gene Regulation ◽  
Transposable Elements ◽  
Specific Gene ◽  
Functional Evaluation ◽  
Mouse Development ◽  
Trophoblast Stem Cells ◽  
Trophoblast Stem ◽  
Gene Regulatory ◽  
Early Mouse

Transposable elements (TEs) are thought to have helped establish gene regulatory networks. Both the embryonic and extraembryonic lineages of the early mouse embryo have seemingly co-opted TEs as enhancers, but there is little evidence that they play significant roles in gene regulation. Here we tested a set of long terminal repeat TE families for roles as enhancers in mouse embryonic and trophoblast stem cells. Epigenomic and transcriptomic data suggested that a large number of TEs helped to establish tissue-specific gene expression programmes. Genetic editing of individual TEs confirmed a subset of these regulatory relationships. However, a wider survey via CRISPR interference of RLTR13D6 elements in embryonic stem cells revealed that only a minority play significant roles in gene regulation. Our results suggest that a subset of TEs are important for gene regulation in early mouse development, and highlight the importance of functional experiments when evaluating gene regulatory roles of TEs.

scholarly journals Functional evaluation of transposable elements as transcriptional enhancers in mouse embryonic and trophoblast stem cells

2018 ◽  
Author(s):  
Christopher D. Todd ◽  
Özgen Deniz ◽  
Miguel R. Branco
Keyword(s):  
Gene Expression ◽  
Stem Cells ◽  
Gene Regulation ◽  
Transposable Elements ◽  
Regulation Of Gene Expression ◽  
Embryonic Stem ◽  
Specific Gene ◽  
Functional Evaluation ◽  
Trophoblast Stem Cells ◽  
Trophoblast Stem

AbstractThe recurrent invasion and expansion of transposable elements (TEs) throughout evolution brought with it a vast array of coding and non-coding sequences that can serve as substrates for natural selection. Namely, TEs are thought to have contributed to the establishment of gene regulatory networks via their cis-acting elements. Both the embryonic and extraembryonic lineages of the early mouse embryo are thought to have benefited from the co-option of TEs as distal enhancer elements. However, there is little to no evidence that these particular TEs play significant roles in the regulation of gene expression. Here we tested for roles of TEs as enhancers in mouse embryonic and trophoblast stem cells by combining bioinformatic analyses with genetic and epigenetic editing experiments. Epigenomic and transcriptomic data from wildtype cells suggested that a large number of TEs played a role in the establishment of highly tissue-specific gene expression programmes. Through genetic editing of individual TEs we confirmed a subset of these regulatory relationships. However, a wider survey via CRISPR interference of RLTR13D6 elements in embryonic stem cells revealed that only a minority play significant roles in gene regulation. Our results suggest that a small proportion of TEs contribute to the mouse pluripotency regulatory network, and highlight the importance of functional experiments when evaluating the role of TEs in gene regulation.

scholarly journals Human trophoblast stem cells: Real or not real?

Placenta ◽  
2017 ◽  
Vol 60 ◽  
pp. S57-S60 ◽  
Author(s):  
Ching-Wen Chang ◽  
Mana M. Parast
Keyword(s):  
Stem Cells ◽  
Human Trophoblast ◽  
Trophoblast Stem Cells ◽  
Trophoblast Stem

Use of Hyperosmolar Stress to Measure Stress-Activated Protein Kinase Activation and Function in Human HTR Cells and Mouse Trophoblast Stem Cells

2007 ◽  
Vol 14 (6) ◽  
pp. 534-547 ◽  
Author(s):  
Wenjing Zhong ◽  
Yufen Xie ◽  
Yingchun Wang ◽  
Jennifer Lewis ◽  
Anna Trostinskaia ◽  
...  
Keyword(s):  
Stem Cells ◽  
Protein Kinase ◽  
Kinase Activation ◽  
Trophoblast Stem Cells ◽  
Trophoblast Stem ◽  
Protein Kinase Activation ◽  
And Function

scholarly journals Histone demethylase JMJD2B/KDM4B regulates transcriptional program via distinctive epigenetic targets and protein interactors for the maintenance of trophoblast stem cells

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Kylie Hin-Man Mak ◽  
Yuk Man Lam ◽  
Ray Kit Ng
Keyword(s):  
Stem Cells ◽  
Transcription Factor ◽  
Cell Fate ◽  
Histone Demethylase ◽  
Gene Promoters ◽  
Transcriptional Program ◽  
Binding Motifs ◽  
Trophoblast Stem Cells ◽  
Trophoblast Stem ◽  
Trophoblast Stem Cell

AbstractTrophoblast stem cell (TSC) is crucial to the formation of placenta in mammals. Histone demethylase JMJD2 (also known as KDM4) family proteins have been previously shown to support self-renewal and differentiation of stem cells. However, their roles in the context of the trophoblast lineage remain unclear. Here, we find that knockdown of Jmjd2b resulted in differentiation of TSCs, suggesting an indispensable role of JMJD2B/KDM4B in maintaining the stemness. Through the integration of transcriptome and ChIP-seq profiling data, we show that JMJD2B is associated with a loss of H3K36me3 in a subset of embryonic lineage genes which are marked by H3K9me3 for stable repression. By characterizing the JMJD2B binding motifs and other transcription factor binding datasets, we discover that JMJD2B forms a protein complex with AP-2 family transcription factor TFAP2C and histone demethylase LSD1. The JMJD2B–TFAP2C–LSD1 complex predominantly occupies active gene promoters, whereas the TFAP2C–LSD1 complex is located at putative enhancers, suggesting that these proteins mediate enhancer–promoter interaction for gene regulation. We conclude that JMJD2B is vital to the TSC transcriptional program and safeguards the trophoblast cell fate via distinctive protein interactors and epigenetic targets.

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