Cargando…
Nucleosomal occupancy changes locally over key regulatory regions during cell differentiation and reprogramming
Chromatin structure determines DNA accessibility. We compare nucleosome occupancy in mouse and human embryonic stem cells (ESCs), induced-pluripotent stem cells (iPSCs) and differentiated cell types using MNase-seq. To address variability inherent in this technique, we developed a bioinformatic appr...
Autores principales: | , , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Pub. Group
2014
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4217530/ https://www.ncbi.nlm.nih.gov/pubmed/25158628 http://dx.doi.org/10.1038/ncomms5719 |
_version_ | 1782342401444020224 |
---|---|
author | West, Jason A. Cook, April Alver, Burak H. Stadtfeld, Matthias Deaton, Aimee M. Hochedlinger, Konrad Park, Peter J. Tolstorukov, Michael Y. Kingston, Robert E. |
author_facet | West, Jason A. Cook, April Alver, Burak H. Stadtfeld, Matthias Deaton, Aimee M. Hochedlinger, Konrad Park, Peter J. Tolstorukov, Michael Y. Kingston, Robert E. |
author_sort | West, Jason A. |
collection | PubMed |
description | Chromatin structure determines DNA accessibility. We compare nucleosome occupancy in mouse and human embryonic stem cells (ESCs), induced-pluripotent stem cells (iPSCs) and differentiated cell types using MNase-seq. To address variability inherent in this technique, we developed a bioinformatic approach to identify regions of difference (RoD) in nucleosome occupancy between pluripotent and somatic cells. Surprisingly, most chromatin remains unchanged; a majority of rearrangements appear to affect a single nucleosome. RoDs are enriched at genes and regulatory elements, including enhancers associated with pluripotency and differentiation. RoDs co-localize with binding sites of key developmental regulators, including the reprogramming factors Klf4, Oct4/Sox2 and c-Myc. Nucleosomal landscapes in ESC enhancers are extensively altered, exhibiting lower nucleosome occupancy in pluripotent cells than in somatic cells. Most changes are reset during reprogramming. We conclude that changes in nucleosome occupancy are a hallmark of cell differentiation and reprogramming and likely identify regulatory regions essential for these processes. |
format | Online Article Text |
id | pubmed-4217530 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2014 |
publisher | Nature Pub. Group |
record_format | MEDLINE/PubMed |
spelling | pubmed-42175302015-02-27 Nucleosomal occupancy changes locally over key regulatory regions during cell differentiation and reprogramming West, Jason A. Cook, April Alver, Burak H. Stadtfeld, Matthias Deaton, Aimee M. Hochedlinger, Konrad Park, Peter J. Tolstorukov, Michael Y. Kingston, Robert E. Nat Commun Article Chromatin structure determines DNA accessibility. We compare nucleosome occupancy in mouse and human embryonic stem cells (ESCs), induced-pluripotent stem cells (iPSCs) and differentiated cell types using MNase-seq. To address variability inherent in this technique, we developed a bioinformatic approach to identify regions of difference (RoD) in nucleosome occupancy between pluripotent and somatic cells. Surprisingly, most chromatin remains unchanged; a majority of rearrangements appear to affect a single nucleosome. RoDs are enriched at genes and regulatory elements, including enhancers associated with pluripotency and differentiation. RoDs co-localize with binding sites of key developmental regulators, including the reprogramming factors Klf4, Oct4/Sox2 and c-Myc. Nucleosomal landscapes in ESC enhancers are extensively altered, exhibiting lower nucleosome occupancy in pluripotent cells than in somatic cells. Most changes are reset during reprogramming. We conclude that changes in nucleosome occupancy are a hallmark of cell differentiation and reprogramming and likely identify regulatory regions essential for these processes. Nature Pub. Group 2014-08-27 /pmc/articles/PMC4217530/ /pubmed/25158628 http://dx.doi.org/10.1038/ncomms5719 Text en Copyright © 2014, Nature Publishing Group, a division of Macmillan Publishers Limited. All Rights Reserved. http://creativecommons.org/licenses/by-nc-sa/4.0/ This work is licensed under a Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by-nc-sa/4.0/ |
spellingShingle | Article West, Jason A. Cook, April Alver, Burak H. Stadtfeld, Matthias Deaton, Aimee M. Hochedlinger, Konrad Park, Peter J. Tolstorukov, Michael Y. Kingston, Robert E. Nucleosomal occupancy changes locally over key regulatory regions during cell differentiation and reprogramming |
title | Nucleosomal occupancy changes locally over key regulatory regions during cell differentiation and reprogramming |
title_full | Nucleosomal occupancy changes locally over key regulatory regions during cell differentiation and reprogramming |
title_fullStr | Nucleosomal occupancy changes locally over key regulatory regions during cell differentiation and reprogramming |
title_full_unstemmed | Nucleosomal occupancy changes locally over key regulatory regions during cell differentiation and reprogramming |
title_short | Nucleosomal occupancy changes locally over key regulatory regions during cell differentiation and reprogramming |
title_sort | nucleosomal occupancy changes locally over key regulatory regions during cell differentiation and reprogramming |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4217530/ https://www.ncbi.nlm.nih.gov/pubmed/25158628 http://dx.doi.org/10.1038/ncomms5719 |
work_keys_str_mv | AT westjasona nucleosomaloccupancychangeslocallyoverkeyregulatoryregionsduringcelldifferentiationandreprogramming AT cookapril nucleosomaloccupancychangeslocallyoverkeyregulatoryregionsduringcelldifferentiationandreprogramming AT alverburakh nucleosomaloccupancychangeslocallyoverkeyregulatoryregionsduringcelldifferentiationandreprogramming AT stadtfeldmatthias nucleosomaloccupancychangeslocallyoverkeyregulatoryregionsduringcelldifferentiationandreprogramming AT deatonaimeem nucleosomaloccupancychangeslocallyoverkeyregulatoryregionsduringcelldifferentiationandreprogramming AT hochedlingerkonrad nucleosomaloccupancychangeslocallyoverkeyregulatoryregionsduringcelldifferentiationandreprogramming AT parkpeterj nucleosomaloccupancychangeslocallyoverkeyregulatoryregionsduringcelldifferentiationandreprogramming AT tolstorukovmichaely nucleosomaloccupancychangeslocallyoverkeyregulatoryregionsduringcelldifferentiationandreprogramming AT kingstonroberte nucleosomaloccupancychangeslocallyoverkeyregulatoryregionsduringcelldifferentiationandreprogramming |