Regulation of the Flt3 gene in haematopoietic stem and early progenitor cells

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Regulation of the Flt3 gene in haematopoietic stem and early progenitor cells. / Volpe, Giacomo; Clarke, Mary; Garcìa, Paloma; Walton, David Scott; Vegiopoulos, Alexandros; Del Pozzo, Walter; O’neill, Laura Patricia; Frampton, Jonathan; Dumon, Stéphanie.

In: PLoS ONE, Vol. 10, No. 9, e0138257, 18.09.2015.

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@article{3f4ffc938fad4a84affd0e8c470ed620,
title = "Regulation of the Flt3 gene in haematopoietic stem and early progenitor cells",
abstract = "The MYB transcription factor plays critical roles in normal and malignant haematopoiesis. We previously showed that MYB was a direct activator of FLT3 expression within the context of acute myeloid leukaemia. During normal haematopoiesis, increasing levels of FLT3 expression determine a strict hierarchy within the haematopoietic stem and early progenitor compartment, which associates with lymphoid and myeloid commitment potential. We use the conditional deletion of the Myb gene to investigate the influence of MYB in Flt3 transcriptional regulation within the haematopoietic stem cell (HSC) hierarchy. In accordance with previous report, in vivo deletion of Myb resulted in rapid biased differentiation of HSC with concomitant loss of proliferation capacity. We find that loss of MYB activity also coincided with decreased FLT3 expression. At the chromatin level, the Flt3 promoter is primed in immature HSC, but occupancy of further intronic elements determines expression. Binding to these locations, MYB and C/EBPα need functional cooperation to activate transcription of the locus. This cooperation is cell context dependent and indicates that MYB and C/EBPα activities are inter-dependent in controlling Flt3 expression to influence lineage commitment of multipotential progenitors.",
keywords = "Bone marrow cells, Hematopoietic stem cells, Stem cells, Flow cytometry, Hematopoiesis, Gene regulation, Cell differentiation, Luciferase",
author = "Giacomo Volpe and Mary Clarke and Paloma Garc{\`i}a and Walton, {David Scott} and Alexandros Vegiopoulos and {Del Pozzo}, Walter and O{\textquoteright}neill, {Laura Patricia} and Jonathan Frampton and St{\'e}phanie Dumon",
year = "2015",
month = sep
day = "18",
doi = "10.1371/journal.pone.0138257",
language = "English",
volume = "10",
journal = "PLoSONE",
issn = "1932-6203",
publisher = "Public Library of Science (PLOS)",
number = "9",

}

RIS

TY - JOUR

T1 - Regulation of the Flt3 gene in haematopoietic stem and early progenitor cells

AU - Volpe, Giacomo

AU - Clarke, Mary

AU - Garcìa, Paloma

AU - Walton, David Scott

AU - Vegiopoulos, Alexandros

AU - Del Pozzo, Walter

AU - O’neill, Laura Patricia

AU - Frampton, Jonathan

AU - Dumon, Stéphanie

PY - 2015/9/18

Y1 - 2015/9/18

N2 - The MYB transcription factor plays critical roles in normal and malignant haematopoiesis. We previously showed that MYB was a direct activator of FLT3 expression within the context of acute myeloid leukaemia. During normal haematopoiesis, increasing levels of FLT3 expression determine a strict hierarchy within the haematopoietic stem and early progenitor compartment, which associates with lymphoid and myeloid commitment potential. We use the conditional deletion of the Myb gene to investigate the influence of MYB in Flt3 transcriptional regulation within the haematopoietic stem cell (HSC) hierarchy. In accordance with previous report, in vivo deletion of Myb resulted in rapid biased differentiation of HSC with concomitant loss of proliferation capacity. We find that loss of MYB activity also coincided with decreased FLT3 expression. At the chromatin level, the Flt3 promoter is primed in immature HSC, but occupancy of further intronic elements determines expression. Binding to these locations, MYB and C/EBPα need functional cooperation to activate transcription of the locus. This cooperation is cell context dependent and indicates that MYB and C/EBPα activities are inter-dependent in controlling Flt3 expression to influence lineage commitment of multipotential progenitors.

AB - The MYB transcription factor plays critical roles in normal and malignant haematopoiesis. We previously showed that MYB was a direct activator of FLT3 expression within the context of acute myeloid leukaemia. During normal haematopoiesis, increasing levels of FLT3 expression determine a strict hierarchy within the haematopoietic stem and early progenitor compartment, which associates with lymphoid and myeloid commitment potential. We use the conditional deletion of the Myb gene to investigate the influence of MYB in Flt3 transcriptional regulation within the haematopoietic stem cell (HSC) hierarchy. In accordance with previous report, in vivo deletion of Myb resulted in rapid biased differentiation of HSC with concomitant loss of proliferation capacity. We find that loss of MYB activity also coincided with decreased FLT3 expression. At the chromatin level, the Flt3 promoter is primed in immature HSC, but occupancy of further intronic elements determines expression. Binding to these locations, MYB and C/EBPα need functional cooperation to activate transcription of the locus. This cooperation is cell context dependent and indicates that MYB and C/EBPα activities are inter-dependent in controlling Flt3 expression to influence lineage commitment of multipotential progenitors.

KW - Bone marrow cells

KW - Hematopoietic stem cells

KW - Stem cells

KW - Flow cytometry

KW - Hematopoiesis

KW - Gene regulation

KW - Cell differentiation

KW - Luciferase

U2 - 10.1371/journal.pone.0138257

DO - 10.1371/journal.pone.0138257

M3 - Article

VL - 10

JO - PLoSONE

JF - PLoSONE

SN - 1932-6203

IS - 9

M1 - e0138257

ER -