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
C2 - 29847803
SN - 2211-1247
VL - 23
SP - 2744
EP - 2757
JO - Cell Reports
JF - Cell Reports
IS - 9
ER -