RUNX1 reshapes the epigenetic landscape at the onset of haematopoiesis

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RUNX1 reshapes the epigenetic landscape at the onset of haematopoiesis. / Lichtinger, Monika; Ingram, Richard; Hannah, Rebecca; Müller, Dorothee; Clarke, Deborah; Assi, Salam A; Lie-A-Ling, Michael; Noailles, Laura; Vijayabaskar, M S; Wu, Mengchu; Tenen, Daniel G; Westhead, David R; Kouskoff, Valerie; Lacaud, Georges; Göttgens, Berthold; Bonifer, Constanze.

In: The EMBO journal, Vol. 31, No. 22, 14.11.2012, p. 4318-4333.

Research output: Contribution to journalArticlepeer-review

Harvard

Lichtinger, M, Ingram, R, Hannah, R, Müller, D, Clarke, D, Assi, SA, Lie-A-Ling, M, Noailles, L, Vijayabaskar, MS, Wu, M, Tenen, DG, Westhead, DR, Kouskoff, V, Lacaud, G, Göttgens, B & Bonifer, C 2012, 'RUNX1 reshapes the epigenetic landscape at the onset of haematopoiesis', The EMBO journal, vol. 31, no. 22, pp. 4318-4333. https://doi.org/10.1038/emboj.2012.275

APA

Lichtinger, M., Ingram, R., Hannah, R., Müller, D., Clarke, D., Assi, S. A., Lie-A-Ling, M., Noailles, L., Vijayabaskar, M. S., Wu, M., Tenen, D. G., Westhead, D. R., Kouskoff, V., Lacaud, G., Göttgens, B., & Bonifer, C. (2012). RUNX1 reshapes the epigenetic landscape at the onset of haematopoiesis. The EMBO journal, 31(22), 4318-4333. https://doi.org/10.1038/emboj.2012.275

Vancouver

Lichtinger M, Ingram R, Hannah R, Müller D, Clarke D, Assi SA et al. RUNX1 reshapes the epigenetic landscape at the onset of haematopoiesis. The EMBO journal. 2012 Nov 14;31(22):4318-4333. https://doi.org/10.1038/emboj.2012.275

Author

Lichtinger, Monika ; Ingram, Richard ; Hannah, Rebecca ; Müller, Dorothee ; Clarke, Deborah ; Assi, Salam A ; Lie-A-Ling, Michael ; Noailles, Laura ; Vijayabaskar, M S ; Wu, Mengchu ; Tenen, Daniel G ; Westhead, David R ; Kouskoff, Valerie ; Lacaud, Georges ; Göttgens, Berthold ; Bonifer, Constanze. / RUNX1 reshapes the epigenetic landscape at the onset of haematopoiesis. In: The EMBO journal. 2012 ; Vol. 31, No. 22. pp. 4318-4333.

Bibtex

@article{c4ed9dbbb2484bd59e1809183302e84c,
title = "RUNX1 reshapes the epigenetic landscape at the onset of haematopoiesis",
abstract = "Cell fate decisions during haematopoiesis are governed by lineage-specific transcription factors, such as RUNX1, SCL/TAL1, FLI1 and C/EBP family members. To gain insight into how these transcription factors regulate the activation of haematopoietic genes during embryonic development, we measured the genome-wide dynamics of transcription factor assembly on their target genes during the RUNX1-dependent transition from haemogenic endothelium (HE) to haematopoietic progenitors. Using a Runx1-/- embryonic stem cell differentiation model expressing an inducible Runx1 gene, we show that in the absence of RUNX1, haematopoietic genes bind SCL/TAL1, FLI1 and C/EBPβ and that this early priming is required for correct temporal expression of the myeloid master regulator PU.1 and its downstream targets. After induction, RUNX1 binds to numerous de novo sites, initiating a local increase in histone acetylation and rapid global alterations in the binding patterns of SCL/TAL1 and FLI1. The acquisition of haematopoietic fate controlled by Runx1 therefore does not represent the establishment of a new regulatory layer on top of a pre-existing HE program but instead entails global reorganization of lineage-specific transcription factor assemblies.",
keywords = "Cell Fate Decisions, Endothelial–Haematopoietic Transition, Haematopoiesis, RUNX1, Transcriptional Programming Of Chromatin",
author = "Monika Lichtinger and Richard Ingram and Rebecca Hannah and Dorothee M{\"u}ller and Deborah Clarke and Assi, {Salam A} and Michael Lie-A-Ling and Laura Noailles and Vijayabaskar, {M S} and Mengchu Wu and Tenen, {Daniel G} and Westhead, {David R} and Valerie Kouskoff and Georges Lacaud and Berthold G{\"o}ttgens and Constanze Bonifer",
year = "2012",
month = nov,
day = "14",
doi = "10.1038/emboj.2012.275",
language = "English",
volume = "31",
pages = "4318--4333",
journal = "The EMBO journal",
issn = "0261-4189",
publisher = "EMBO Press",
number = "22",

}

RIS

TY - JOUR

T1 - RUNX1 reshapes the epigenetic landscape at the onset of haematopoiesis

AU - Lichtinger, Monika

AU - Ingram, Richard

AU - Hannah, Rebecca

AU - Müller, Dorothee

AU - Clarke, Deborah

AU - Assi, Salam A

AU - Lie-A-Ling, Michael

AU - Noailles, Laura

AU - Vijayabaskar, M S

AU - Wu, Mengchu

AU - Tenen, Daniel G

AU - Westhead, David R

AU - Kouskoff, Valerie

AU - Lacaud, Georges

AU - Göttgens, Berthold

AU - Bonifer, Constanze

PY - 2012/11/14

Y1 - 2012/11/14

N2 - Cell fate decisions during haematopoiesis are governed by lineage-specific transcription factors, such as RUNX1, SCL/TAL1, FLI1 and C/EBP family members. To gain insight into how these transcription factors regulate the activation of haematopoietic genes during embryonic development, we measured the genome-wide dynamics of transcription factor assembly on their target genes during the RUNX1-dependent transition from haemogenic endothelium (HE) to haematopoietic progenitors. Using a Runx1-/- embryonic stem cell differentiation model expressing an inducible Runx1 gene, we show that in the absence of RUNX1, haematopoietic genes bind SCL/TAL1, FLI1 and C/EBPβ and that this early priming is required for correct temporal expression of the myeloid master regulator PU.1 and its downstream targets. After induction, RUNX1 binds to numerous de novo sites, initiating a local increase in histone acetylation and rapid global alterations in the binding patterns of SCL/TAL1 and FLI1. The acquisition of haematopoietic fate controlled by Runx1 therefore does not represent the establishment of a new regulatory layer on top of a pre-existing HE program but instead entails global reorganization of lineage-specific transcription factor assemblies.

AB - Cell fate decisions during haematopoiesis are governed by lineage-specific transcription factors, such as RUNX1, SCL/TAL1, FLI1 and C/EBP family members. To gain insight into how these transcription factors regulate the activation of haematopoietic genes during embryonic development, we measured the genome-wide dynamics of transcription factor assembly on their target genes during the RUNX1-dependent transition from haemogenic endothelium (HE) to haematopoietic progenitors. Using a Runx1-/- embryonic stem cell differentiation model expressing an inducible Runx1 gene, we show that in the absence of RUNX1, haematopoietic genes bind SCL/TAL1, FLI1 and C/EBPβ and that this early priming is required for correct temporal expression of the myeloid master regulator PU.1 and its downstream targets. After induction, RUNX1 binds to numerous de novo sites, initiating a local increase in histone acetylation and rapid global alterations in the binding patterns of SCL/TAL1 and FLI1. The acquisition of haematopoietic fate controlled by Runx1 therefore does not represent the establishment of a new regulatory layer on top of a pre-existing HE program but instead entails global reorganization of lineage-specific transcription factor assemblies.

KW - Cell Fate Decisions

KW - Endothelial–Haematopoietic Transition

KW - Haematopoiesis

KW - RUNX1

KW - Transcriptional Programming Of Chromatin

U2 - 10.1038/emboj.2012.275

DO - 10.1038/emboj.2012.275

M3 - Article

C2 - 23064151

VL - 31

SP - 4318

EP - 4333

JO - The EMBO journal

JF - The EMBO journal

SN - 0261-4189

IS - 22

ER -