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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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  1. Nodal Signaling Regulates Germ Cell Development and Establishment of Seminiferous Cords in the Human Fetal Testis

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  2. Gamma-Aminobutyric Acid Signaling in Brown Adipose Tissue Promotes Systemic Metabolic Derangement in Obesity

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  3. Differences in Cell Cycle Status Underlie Transcriptional Heterogeneity in the HSC Compartment

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  4. A Specific PfEMP1 Is Expressed in P. falciparum Sporozoites and Plays a Role in Hepatocyte Infection

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  5. The Apolipoprotein M/S1P Axis Controls Triglyceride Metabolism and Brown Fat Activity

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  1. The splicing factor RBM25 controls MYC activity in acute myeloid leukemia

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  2. BloodSpot: a database of healthy and malignant haematopoiesis updated with purified and single cell mRNA sequencing profiles

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  3. Genetic, Clinical, and Environmental Factors Associated With Persistent Atopic Dermatitis in Childhood

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  4. Leukemogenic nucleophosmin mutation disrupts the transcription factor hub regulating granulo-monocytic fates

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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.

Original languageEnglish
JournalCell Reports
Volume23
Issue number9
Pages (from-to)2744-2757
Number of pages14
DOIs
Publication statusPublished - 29 May 2018

ID: 54443524