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Comparison of reprogramming factor targets reveals both species-specific and conserved mechanisms in early iPSC reprogramming
BACKGROUND: Both human and mouse fibroblasts can be reprogrammed to pluripotency with Oct4, Sox2, Klf4, and c-Myc (OSKM) transcription factors. While both systems generate pluripotency, human reprogramming takes considerably longer than mouse. RESULTS: To assess additional similarities and differenc...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2018
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6303873/ https://www.ncbi.nlm.nih.gov/pubmed/30577748 http://dx.doi.org/10.1186/s12864-018-5326-1 |
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author | Fu, Kai Chronis, Constantinos Soufi, Abdenour Bonora, Giancarlo Edwards, Miguel Smale, Stephen T. Zaret, Kenneth S. Plath, Kathrin Pellegrini, Matteo |
author_facet | Fu, Kai Chronis, Constantinos Soufi, Abdenour Bonora, Giancarlo Edwards, Miguel Smale, Stephen T. Zaret, Kenneth S. Plath, Kathrin Pellegrini, Matteo |
author_sort | Fu, Kai |
collection | PubMed |
description | BACKGROUND: Both human and mouse fibroblasts can be reprogrammed to pluripotency with Oct4, Sox2, Klf4, and c-Myc (OSKM) transcription factors. While both systems generate pluripotency, human reprogramming takes considerably longer than mouse. RESULTS: To assess additional similarities and differences, we sought to compare the binding of the reprogramming factors between the two systems. In human fibroblasts, the OSK factors initially target many more closed chromatin sites compared to mouse. Despite this difference, the intra- and intergenic distribution of target sites, target genes, primary binding motifs, and combinatorial binding patterns between the reprogramming factors are largely shared. However, while many OSKM binding events in early mouse cell reprogramming occur in syntenic regions, only a limited number is conserved in human. CONCLUSIONS: Our findings suggest similar general effects of OSKM binding across these two species, even though the detailed regulatory networks have diverged significantly. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s12864-018-5326-1) contains supplementary material, which is available to authorized users. |
format | Online Article Text |
id | pubmed-6303873 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-63038732018-12-31 Comparison of reprogramming factor targets reveals both species-specific and conserved mechanisms in early iPSC reprogramming Fu, Kai Chronis, Constantinos Soufi, Abdenour Bonora, Giancarlo Edwards, Miguel Smale, Stephen T. Zaret, Kenneth S. Plath, Kathrin Pellegrini, Matteo BMC Genomics Research Article BACKGROUND: Both human and mouse fibroblasts can be reprogrammed to pluripotency with Oct4, Sox2, Klf4, and c-Myc (OSKM) transcription factors. While both systems generate pluripotency, human reprogramming takes considerably longer than mouse. RESULTS: To assess additional similarities and differences, we sought to compare the binding of the reprogramming factors between the two systems. In human fibroblasts, the OSK factors initially target many more closed chromatin sites compared to mouse. Despite this difference, the intra- and intergenic distribution of target sites, target genes, primary binding motifs, and combinatorial binding patterns between the reprogramming factors are largely shared. However, while many OSKM binding events in early mouse cell reprogramming occur in syntenic regions, only a limited number is conserved in human. CONCLUSIONS: Our findings suggest similar general effects of OSKM binding across these two species, even though the detailed regulatory networks have diverged significantly. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s12864-018-5326-1) contains supplementary material, which is available to authorized users. BioMed Central 2018-12-22 /pmc/articles/PMC6303873/ /pubmed/30577748 http://dx.doi.org/10.1186/s12864-018-5326-1 Text en © The Author(s). 2018 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated. |
spellingShingle | Research Article Fu, Kai Chronis, Constantinos Soufi, Abdenour Bonora, Giancarlo Edwards, Miguel Smale, Stephen T. Zaret, Kenneth S. Plath, Kathrin Pellegrini, Matteo Comparison of reprogramming factor targets reveals both species-specific and conserved mechanisms in early iPSC reprogramming |
title | Comparison of reprogramming factor targets reveals both species-specific and conserved mechanisms in early iPSC reprogramming |
title_full | Comparison of reprogramming factor targets reveals both species-specific and conserved mechanisms in early iPSC reprogramming |
title_fullStr | Comparison of reprogramming factor targets reveals both species-specific and conserved mechanisms in early iPSC reprogramming |
title_full_unstemmed | Comparison of reprogramming factor targets reveals both species-specific and conserved mechanisms in early iPSC reprogramming |
title_short | Comparison of reprogramming factor targets reveals both species-specific and conserved mechanisms in early iPSC reprogramming |
title_sort | comparison of reprogramming factor targets reveals both species-specific and conserved mechanisms in early ipsc reprogramming |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6303873/ https://www.ncbi.nlm.nih.gov/pubmed/30577748 http://dx.doi.org/10.1186/s12864-018-5326-1 |
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