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Chromatin module inference on cellular trajectories identifies key transition points and poised epigenetic states in diverse developmental processes
Changes in chromatin state play important roles in cell fate transitions. Current computational approaches to analyze chromatin modifications across multiple cell types do not model how the cell types are related on a lineage or over time. To overcome this limitation, we developed a method called Ch...
Autores principales: | , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Cold Spring Harbor Laboratory Press
2017
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5495076/ https://www.ncbi.nlm.nih.gov/pubmed/28424352 http://dx.doi.org/10.1101/gr.215004.116 |
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author | Roy, Sushmita Sridharan, Rupa |
author_facet | Roy, Sushmita Sridharan, Rupa |
author_sort | Roy, Sushmita |
collection | PubMed |
description | Changes in chromatin state play important roles in cell fate transitions. Current computational approaches to analyze chromatin modifications across multiple cell types do not model how the cell types are related on a lineage or over time. To overcome this limitation, we developed a method called Chromatin Module INference on Trees (CMINT), a probabilistic clustering approach to systematically capture chromatin state dynamics across multiple cell types. Compared to existing approaches, CMINT can handle complex lineage topologies, capture higher quality clusters, and reliably detect chromatin transitions between cell types. We applied CMINT to gain novel insights in two complex processes: reprogramming to induced pluripotent stem cells (iPSCs) and hematopoiesis. In reprogramming, chromatin changes could occur without large gene expression changes, different combinations of activating marks were associated with specific reprogramming factors, there was an order of acquisition of chromatin marks at pluripotency loci, and multivalent states (comprising previously undetermined combinations of activating and repressive histone modifications) were enriched for CTCF. In the hematopoietic system, we defined critical decision points in the lineage tree, identified regulatory elements that were enriched in cell-type–specific regions, and found that the underlying chromatin state was achieved by specific erasure of preexisting chromatin marks in the precursor cell or by de novo assembly. Our method provides a systematic approach to model the dynamics of chromatin state to provide novel insights into the relationships among cell types in diverse cell-fate specification processes. |
format | Online Article Text |
id | pubmed-5495076 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
publisher | Cold Spring Harbor Laboratory Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-54950762017-07-18 Chromatin module inference on cellular trajectories identifies key transition points and poised epigenetic states in diverse developmental processes Roy, Sushmita Sridharan, Rupa Genome Res Method Changes in chromatin state play important roles in cell fate transitions. Current computational approaches to analyze chromatin modifications across multiple cell types do not model how the cell types are related on a lineage or over time. To overcome this limitation, we developed a method called Chromatin Module INference on Trees (CMINT), a probabilistic clustering approach to systematically capture chromatin state dynamics across multiple cell types. Compared to existing approaches, CMINT can handle complex lineage topologies, capture higher quality clusters, and reliably detect chromatin transitions between cell types. We applied CMINT to gain novel insights in two complex processes: reprogramming to induced pluripotent stem cells (iPSCs) and hematopoiesis. In reprogramming, chromatin changes could occur without large gene expression changes, different combinations of activating marks were associated with specific reprogramming factors, there was an order of acquisition of chromatin marks at pluripotency loci, and multivalent states (comprising previously undetermined combinations of activating and repressive histone modifications) were enriched for CTCF. In the hematopoietic system, we defined critical decision points in the lineage tree, identified regulatory elements that were enriched in cell-type–specific regions, and found that the underlying chromatin state was achieved by specific erasure of preexisting chromatin marks in the precursor cell or by de novo assembly. Our method provides a systematic approach to model the dynamics of chromatin state to provide novel insights into the relationships among cell types in diverse cell-fate specification processes. Cold Spring Harbor Laboratory Press 2017-07 /pmc/articles/PMC5495076/ /pubmed/28424352 http://dx.doi.org/10.1101/gr.215004.116 Text en © 2017 Roy and Sridharan; Published by Cold Spring Harbor Laboratory Press http://creativecommons.org/licenses/by/4.0/ This article, published in Genome Research, is available under a Creative Commons License (Attribution 4.0 International), as described at http://creativecommons.org/licenses/by/4.0/. |
spellingShingle | Method Roy, Sushmita Sridharan, Rupa Chromatin module inference on cellular trajectories identifies key transition points and poised epigenetic states in diverse developmental processes |
title | Chromatin module inference on cellular trajectories identifies key transition points and poised epigenetic states in diverse developmental processes |
title_full | Chromatin module inference on cellular trajectories identifies key transition points and poised epigenetic states in diverse developmental processes |
title_fullStr | Chromatin module inference on cellular trajectories identifies key transition points and poised epigenetic states in diverse developmental processes |
title_full_unstemmed | Chromatin module inference on cellular trajectories identifies key transition points and poised epigenetic states in diverse developmental processes |
title_short | Chromatin module inference on cellular trajectories identifies key transition points and poised epigenetic states in diverse developmental processes |
title_sort | chromatin module inference on cellular trajectories identifies key transition points and poised epigenetic states in diverse developmental processes |
topic | Method |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5495076/ https://www.ncbi.nlm.nih.gov/pubmed/28424352 http://dx.doi.org/10.1101/gr.215004.116 |
work_keys_str_mv | AT roysushmita chromatinmoduleinferenceoncellulartrajectoriesidentifieskeytransitionpointsandpoisedepigeneticstatesindiversedevelopmentalprocesses AT sridharanrupa chromatinmoduleinferenceoncellulartrajectoriesidentifieskeytransitionpointsandpoisedepigeneticstatesindiversedevelopmentalprocesses |