scholarly journals Widespread conservation of chromatin accessibility patterns and transcription factor binding in human and chimpanzee induced pluripotent stem cells

2018 ◽  
Author(s):  
Irene Gallego Romero ◽  
Shyam Gopalakrishnan ◽  
Yoav Gilad
Keyword(s):  
Stem Cells ◽  
Transcription Factor ◽  
Induced Pluripotent Stem Cells ◽  
Pluripotent Stem Cells ◽  
Related Species ◽  
Transcription Factor Binding ◽  
Chromatin Accessibility ◽  
Closely Related Species ◽  
Factor Binding ◽  
Induced Pluripotent

AbstractChanges in gene regulation have been shown to contribute to phenotypic differences between closely related species, most notably in primates. It is likely that a subset of inter-species regulatory differences can be explained by changes in chromatin accessibility and transcription factor binding, yet there is a paucity of comparative data sets with which to investigate this. Using ATAC-seq, we profiled genome-wide chromatin accessibility in a matched set of 6 human and 6 chimpanzee (Pan troglodytes, our closest living relative) induced pluripotent stem cells from which we have previously collected gene expression data. We examined chromatin accessibility patterns near 20,745 orthologous transcriptions start sites and used a footprinting algorithm to predict transcription factor binding activity in each species. We found that the majority of chromatin accessibility patterns and transcription factor activity are conserved between these two closely related species. Interestingly, interspecies divergence in chromatin accessibility and transcription factor binding in pluripotent cells appear to contribute not to differences in the pluripotent state, but to downstream developmental processes. Put together, our findings suggest that the pluripotent state is extremely stable and potentially subject to stronger evolutionary constraint than other somatic tissues.

scholarly journals Single Transcription Factor Reprogramming of Hair Follicle Dermal Papilla Cells to Induced Pluripotent Stem Cells

Stem Cells ◽  
2011 ◽  
Vol 29 (6) ◽  
pp. 964-971 ◽  
Author(s):  
Su-Yi Tsai ◽  
Britta Am Bouwman ◽  
Yen-Sin Ang ◽  
Soo Jeong Kim ◽  
Dung-Fang Lee ◽  
...  
Keyword(s):  
Stem Cells ◽  
Transcription Factor ◽  
Induced Pluripotent Stem Cells ◽  
Hair Follicle ◽  
Pluripotent Stem Cells ◽  
Dermal Papilla ◽  
Dermal Papilla Cells ◽  
Induced Pluripotent

scholarly journals Finding Transcription Factor Binding Motifs for Coregulated Genes by Combining Sequence Overrepresentation with Cross-Species Conservation

2012 ◽  
Vol 2012 ◽  
pp. 1-18 ◽  
Author(s):  
Hui Jia ◽  
Jinming Li
Keyword(s):  
Transcription Factor ◽  
Related Species ◽  
Transcription Factor Binding ◽  
Transcriptional Factors ◽  
Transcriptional Factor ◽  
Motif Finding ◽  
Closely Related Species ◽  
Binding Motifs ◽  
Factor Binding ◽  
Transcription Factor Binding Motifs

Novel computational methods for finding transcription factor binding motifs have long been sought due to tedious work of experimentally identifying them. However, the current prevailing methods yield a large number of false positive predictions due to the short, variable nature of transcriptional factor binding sites (TFBSs). We proposed here a method that combines sequence overrepresentation and cross-species sequence conservation to detect TFBSs in upstream regions of a given set of coregulated genes. We applied the method to 35S. cerevisiaetranscriptional factors with known DNA binding motifs (with the support of orthologous sequences from genomes ofS. mikatae,S. bayanus, andS. paradoxus), and the proposed method outperformed the single-genome-based motif finding methodsMEMEandAlignACEas well as the multiple-genome-based methodsPHYMEandFootprinterfor the majority of these transcriptional factors. Compared with the prevailing motif finding software, our method has some advantages in finding transcriptional factor binding motifs for potential coregulated genes if the gene upstream sequences of multiple closely related species are available. Although we used yeast genomes to assess our method in this study, it might also be applied to other organisms if suitable related species are available and the upstream sequences of coregulated genes can be obtained for the multiple closely related species.

TBX18 transcription factor overexpression in human-induced pluripotent stem cells increases their differentiation into pacemaker-like cells

2018 ◽  
Vol 234 (2) ◽  
pp. 1534-1546 ◽  
Author(s):  
Armita M. Gorabi ◽  
Saeideh Hajighasemi ◽  
Hossein A. Tafti ◽  
Amir Atashi ◽  
Masoud Soleimani ◽  
...  
Keyword(s):  
Stem Cells ◽  
Transcription Factor ◽  
Induced Pluripotent Stem Cells ◽  
Pluripotent Stem Cells ◽  
Induced Pluripotent

scholarly journals SUMO maintains the chromatin environment of human induced pluripotent stem cells

2020 ◽  
Author(s):  
Barbara Mojsa ◽  
Michael H. Tatham ◽  
Lindsay Davidson ◽  
Magda Liczmanska ◽  
Jane E. Wright ◽  
...  
Keyword(s):  
Stem Cells ◽  
Induced Pluripotent Stem Cells ◽  
Cell Fate ◽  
Pluripotent Stem Cells ◽  
Transcriptional Start Site ◽  
Chromatin Accessibility ◽  
Covalent Attachment ◽  
Cell Fate Decisions ◽  
Sumo Modification ◽  
Induced Pluripotent

AbstractPluripotent stem cells represent a powerful system to identify the mechanisms governing cell fate decisions during early mammalian development. Covalent attachment of the Small Ubiquitin Like Modifier (SUMO) to proteins has emerged as an important factor in stem cell maintenance. Here we show that SUMO is required to maintain stem cells in their pluripotent state and identify many chromatin-associated proteins as bona fide SUMO substrates in human induced pluripotent stem cells (hiPSCs). Loss of SUMO increases chromatin accessibility and expression of long non-coding RNAs and human endogenous retroviral elements, indicating a role for the SUMO modification of SETDB1 and a large TRIM28 centric network of zinc finger proteins in silencing of these elements. While most protein coding genes are unaffected, the Preferentially Expressed Antigen of Melanoma (PRAME) gene locus becomes more accessible and transcription is dramatically increased after inhibition of SUMO modification. When PRAME is silent, a peak of SUMO over the transcriptional start site overlaps with ChIP-seq peaks for cohesin, RNA pol II, CTCF and ZNF143, with the latter two heavily modified by SUMO. These associations suggest that silencing of the PRAME gene is maintained by the influence of SUMO on higher order chromatin structure. Our data indicate that SUMO modification plays an important role in hiPSCs by repressing genes that disrupt pluripotency networks or drive differentiation.

scholarly journals Current understanding and future perspectives of the roles of sirtuins in the reprogramming and differentiation of pluripotent stem cells

2018 ◽  
Vol 243 (6) ◽  
pp. 563-575 ◽  
Author(s):  
Yi-Chao Hsu ◽  
Yu-Ting Wu ◽  
Chia-Ling Tsai ◽  
Yau-Huei Wei
Keyword(s):  
Stem Cells ◽  
Transcription Factor ◽  
Stem Cell ◽  
Induced Pluripotent Stem Cells ◽  
Pluripotent Stem Cells ◽  
Somatic Cells ◽  
Stem Cell Differentiation ◽  
Ppar Gamma ◽  
Metabolic Reprogramming ◽  
Induced Pluripotent

In mammalian cells, there are seven members of the sirtuin protein family (SIRT1–7). SIRT1, SIRT6, and SIRT7 catalyze posttranslational modification of proteins in the nucleus, SIRT3, SIRT4, and SIRT5 are in the mitochondria and SIRT2 is in the cytosol. SIRT1 can deacetylate the transcription factor SOX2 and regulate induced pluripotent stem cells (iPSCs) reprogramming through the miR-34a–SIRT1–p53 axis. SIRT2 can regulate the function of pluripotent stem cells through GSK3β. SIRT3 can positively regulate PPAR gamma coactivator 1-alpha (PGC-1α) expression during the differentiation of stem cells. SIRT4 has no direct role in regulating reprogramming but may have the potential to prevent senescence of somatic cells and to facilitate the reprogramming of iPSCs. SIRT5 can deacetylate STAT3, which is an important transcription factor in regulating pluripotency and differentiation of stem cells. SIRT6 can enhance the reprogramming efficiency of iPSCs from aged skin fibroblasts through miR-766 and increase the expression levels of the reprogramming genes including Sox2, Oct4, and Nanog through acetylation of histone H3 lysine 56. SIRT7 plays a regulatory role in the process of mesenchymal-to-epithelial transition (MET), which has been suggested to be a crucial process in the generation of iPSCs from fibroblasts. In this review, we summarize recent findings of the roles of sirtuins in the metabolic reprogramming and differentiation of stem cells and discuss the bidirectional changes in the gene expression and activities of sirtuins in the commitment of differentiation of mesenchymal stem cells (MSCs) and reprogramming of somatic cells to iPSCs, respectively. Thus, understanding the molecular basis of the interplay between different sirtuins and mitochondrial function will provide new insights into the regulation of differentiation of stem cells and iPSCs formation, respectively, and may help design effective stem cell therapies for regenerative medicine. Impact statement This is an extensive review of the recent advances in our understanding of the roles of some members of the sirtuins family, such as SIRT1, SIRT2, SIRT3, and SIRT6, in the regulation of intermediary metabolism during stem cell differentiation and in the reprogramming of somatic cells to form induced pluripotent stem cells (iPSCs). This article provides an updated integrated view on the mechanisms by which sirtuins-mediated posttranslational protein modifications regulate mitochondrial biogenesis, bioenergetics, and antioxidant defense in the maintenance and differentiation of stem cells and in iPSCs formation, respectively.

Sign in / Sign up

Export Citation Format

Share Document