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Active enhancers are delineated de novo during hematopoiesis, with limited lineage fidelity among specified primary blood cells

Tissues may adopt diverse strategies to establish specific transcriptional programs in daughter lineages. In intestinal crypts, enhancers for genes expressed in both major cell types appear broadly permissive in stem and specified progenitor cells. In blood, another self-renewing tissue, it is uncle...

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Autores principales: Luyten, Annouck, Zang, Chongzhi, Liu, X. Shirley, Shivdasani, Ramesh A.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Cold Spring Harbor Laboratory Press 2014
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4197967/
https://www.ncbi.nlm.nih.gov/pubmed/25128499
http://dx.doi.org/10.1101/gad.240101.114
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author Luyten, Annouck
Zang, Chongzhi
Liu, X. Shirley
Shivdasani, Ramesh A.
author_facet Luyten, Annouck
Zang, Chongzhi
Liu, X. Shirley
Shivdasani, Ramesh A.
author_sort Luyten, Annouck
collection PubMed
description Tissues may adopt diverse strategies to establish specific transcriptional programs in daughter lineages. In intestinal crypts, enhancers for genes expressed in both major cell types appear broadly permissive in stem and specified progenitor cells. In blood, another self-renewing tissue, it is unclear when chromatin becomes permissive for transcription of genes expressed in distinct terminal lineages. Using chromatin immunoprecipitation (ChIP) combined with deep sequencing (ChIP-seq) to profile activating histone marks, we studied enhancer dynamics in primary mouse blood stem, progenitor, and specified cells. Stem and multipotent progenitor cells show scant H3K4me2 marking at enhancers bound by specific transcription factors in their committed progeny. Rather, enhancers are modulated dynamically and serially, with substantial loss and gain of H3K4me2, at each cellular transition. Quantitative analysis of these dynamics accurately modeled hematopoiesis according to Waddington’s notion of epigenotypes. Delineation of enhancers in terminal blood lineages coincides with cell specification, and enhancers active in single lineages show well-positioned H3K4me2- and H3K27ac-marked nucleosomes and DNaseI hypersensitivity in other cell types, revealing limited lineage fidelity. These findings demonstrate that enhancer chronology in blood cells differs markedly from that in intestinal crypts. Chromatin dynamics in hematopoiesis provide a useful foundation to consider classical observations such as cellular reprogramming and multilineage locus priming.
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spelling pubmed-41979672015-02-15 Active enhancers are delineated de novo during hematopoiesis, with limited lineage fidelity among specified primary blood cells Luyten, Annouck Zang, Chongzhi Liu, X. Shirley Shivdasani, Ramesh A. Genes Dev Resource/Methodology Tissues may adopt diverse strategies to establish specific transcriptional programs in daughter lineages. In intestinal crypts, enhancers for genes expressed in both major cell types appear broadly permissive in stem and specified progenitor cells. In blood, another self-renewing tissue, it is unclear when chromatin becomes permissive for transcription of genes expressed in distinct terminal lineages. Using chromatin immunoprecipitation (ChIP) combined with deep sequencing (ChIP-seq) to profile activating histone marks, we studied enhancer dynamics in primary mouse blood stem, progenitor, and specified cells. Stem and multipotent progenitor cells show scant H3K4me2 marking at enhancers bound by specific transcription factors in their committed progeny. Rather, enhancers are modulated dynamically and serially, with substantial loss and gain of H3K4me2, at each cellular transition. Quantitative analysis of these dynamics accurately modeled hematopoiesis according to Waddington’s notion of epigenotypes. Delineation of enhancers in terminal blood lineages coincides with cell specification, and enhancers active in single lineages show well-positioned H3K4me2- and H3K27ac-marked nucleosomes and DNaseI hypersensitivity in other cell types, revealing limited lineage fidelity. These findings demonstrate that enhancer chronology in blood cells differs markedly from that in intestinal crypts. Chromatin dynamics in hematopoiesis provide a useful foundation to consider classical observations such as cellular reprogramming and multilineage locus priming. Cold Spring Harbor Laboratory Press 2014-08-15 /pmc/articles/PMC4197967/ /pubmed/25128499 http://dx.doi.org/10.1101/gad.240101.114 Text en © 2014 Luyten et al.; Published by Cold Spring Harbor Laboratory Press http://creativecommons.org/licenses/by-nc/4.0/ This article is distributed exclusively by Cold Spring Harbor Laboratory Press for the first six months after the full-issue publication date (see http://genesdev.cshlp.org/site/misc/terms.xhtml). After six months, it is available under a Creative Commons License (Attribution-NonCommercial 4.0 International), as described at http://creativecommons.org/licenses/by-nc/4.0/.
spellingShingle Resource/Methodology
Luyten, Annouck
Zang, Chongzhi
Liu, X. Shirley
Shivdasani, Ramesh A.
Active enhancers are delineated de novo during hematopoiesis, with limited lineage fidelity among specified primary blood cells
title Active enhancers are delineated de novo during hematopoiesis, with limited lineage fidelity among specified primary blood cells
title_full Active enhancers are delineated de novo during hematopoiesis, with limited lineage fidelity among specified primary blood cells
title_fullStr Active enhancers are delineated de novo during hematopoiesis, with limited lineage fidelity among specified primary blood cells
title_full_unstemmed Active enhancers are delineated de novo during hematopoiesis, with limited lineage fidelity among specified primary blood cells
title_short Active enhancers are delineated de novo during hematopoiesis, with limited lineage fidelity among specified primary blood cells
title_sort active enhancers are delineated de novo during hematopoiesis, with limited lineage fidelity among specified primary blood cells
topic Resource/Methodology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4197967/
https://www.ncbi.nlm.nih.gov/pubmed/25128499
http://dx.doi.org/10.1101/gad.240101.114
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