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Enhancer and Transcription Factor Dynamics during Myeloid Differentiation Reveal an Early Differentiation Block in Cebpa null Progenitors

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@article{2c626b28ac2a427c82069ce84b5b9f61,
title = "Enhancer and Transcription Factor Dynamics during Myeloid Differentiation Reveal an Early Differentiation Block in Cebpa null Progenitors",
abstract = "Transcription factors PU.1 and CEBPA are required for the proper coordination of enhancer activity during granulocytic-monocytic (GM) lineage differentiation to form myeloid cells. However, precisely how these factors control the chronology of enhancer establishment during differentiation is not known. Through integrated analyses of enhancer dynamics, transcription factor binding, and proximal gene expression during successive stages of murine GM-lineage differentiation, we unravel the distinct kinetics by which PU.1 and CEBPA coordinate GM enhancer activity. We find no evidence of a pioneering function of PU.1 during late GM-lineage differentiation. Instead, we delineate a set of enhancers that gain accessibility in a CEBPA-dependent manner, suggesting a pioneering function of CEBPA. Analyses of Cebpa null bone marrow demonstrate that CEBPA controls PU.1 levels and, unexpectedly, that the loss of CEBPA results in an early differentiation block. Taken together, our data provide insights into how PU.1 and CEBPA functionally interact to drive GM-lineage differentiation.",
author = "Sachin Pundhir and Lauridsen, {Felicia Kathrine Bratt} and Schuster, {Mikkel Bruhn} and Jakobsen, {Janus Schou} and Ying Ge and Schoof, {Erwin Marten} and Nicolas Rapin and Johannes Waage and Hasemann, {Marie Sigurd} and Porse, {Bo Torben}",
note = "Copyright {\circledC} 2018 The Author(s). Published by Elsevier Inc. All rights reserved.",
year = "2018",
month = "5",
day = "29",
doi = "10.1016/j.celrep.2018.05.012",
language = "English",
volume = "23",
pages = "2744--2757",
journal = "Cell Reports",
publisher = "Cell Press",
number = "9",

}

RIS

TY - JOUR

T1 - Enhancer and Transcription Factor Dynamics during Myeloid Differentiation Reveal an Early Differentiation Block in Cebpa null Progenitors

AU - Pundhir, Sachin

AU - Lauridsen, Felicia Kathrine Bratt

AU - Schuster, Mikkel Bruhn

AU - Jakobsen, Janus Schou

AU - Ge, Ying

AU - Schoof, Erwin Marten

AU - Rapin, Nicolas

AU - Waage, Johannes

AU - Hasemann, Marie Sigurd

AU - Porse, Bo Torben

N1 - Copyright © 2018 The Author(s). Published by Elsevier Inc. All rights reserved.

PY - 2018/5/29

Y1 - 2018/5/29

N2 - Transcription factors PU.1 and CEBPA are required for the proper coordination of enhancer activity during granulocytic-monocytic (GM) lineage differentiation to form myeloid cells. However, precisely how these factors control the chronology of enhancer establishment during differentiation is not known. Through integrated analyses of enhancer dynamics, transcription factor binding, and proximal gene expression during successive stages of murine GM-lineage differentiation, we unravel the distinct kinetics by which PU.1 and CEBPA coordinate GM enhancer activity. We find no evidence of a pioneering function of PU.1 during late GM-lineage differentiation. Instead, we delineate a set of enhancers that gain accessibility in a CEBPA-dependent manner, suggesting a pioneering function of CEBPA. Analyses of Cebpa null bone marrow demonstrate that CEBPA controls PU.1 levels and, unexpectedly, that the loss of CEBPA results in an early differentiation block. Taken together, our data provide insights into how PU.1 and CEBPA functionally interact to drive GM-lineage differentiation.

AB - Transcription factors PU.1 and CEBPA are required for the proper coordination of enhancer activity during granulocytic-monocytic (GM) lineage differentiation to form myeloid cells. However, precisely how these factors control the chronology of enhancer establishment during differentiation is not known. Through integrated analyses of enhancer dynamics, transcription factor binding, and proximal gene expression during successive stages of murine GM-lineage differentiation, we unravel the distinct kinetics by which PU.1 and CEBPA coordinate GM enhancer activity. We find no evidence of a pioneering function of PU.1 during late GM-lineage differentiation. Instead, we delineate a set of enhancers that gain accessibility in a CEBPA-dependent manner, suggesting a pioneering function of CEBPA. Analyses of Cebpa null bone marrow demonstrate that CEBPA controls PU.1 levels and, unexpectedly, that the loss of CEBPA results in an early differentiation block. Taken together, our data provide insights into how PU.1 and CEBPA functionally interact to drive GM-lineage differentiation.

U2 - 10.1016/j.celrep.2018.05.012

DO - 10.1016/j.celrep.2018.05.012

M3 - Journal article

VL - 23

SP - 2744

EP - 2757

JO - Cell Reports

JF - Cell Reports

IS - 9

ER -

ID: 54443524