The MADS transcription factor Mef2c is a pivotal modulator of myeloid cell fate.
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The MADS transcription factor Mef2c is a pivotal modulator of myeloid cell fate. / Schüler, Andrea; Schwieger, Maike; Engelmann, Afra; Riecken, Kristoffer; Horn, Stefan; Müller, Ursula; Arnold, Michael A; Olson, Eric N; Stocking, Carol.
in: BLOOD, Jahrgang 111, Nr. 9, 9, 2008, S. 4532-4541.Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung
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T1 - The MADS transcription factor Mef2c is a pivotal modulator of myeloid cell fate.
AU - Schüler, Andrea
AU - Schwieger, Maike
AU - Engelmann, Afra
AU - Riecken, Kristoffer
AU - Horn, Stefan
AU - Müller, Ursula
AU - Arnold, Michael A
AU - Olson, Eric N
AU - Stocking, Carol
PY - 2008
Y1 - 2008
N2 - Mef2c is a MADS (MCM1-agamous-deficient serum response factor) transcription factor best known for its role in muscle and cardiovascular development. A causal role of up-regulated MEF2C expression in myelomonocytic acute myeloid leukemia (AML) has recently been demonstrated. Due to the pronounced monocytic component observed in Mef2c-induced AML, this study was designed to assess the importance of Mef2c in normal myeloid differentiation. Analysis of bone marrow (BM) cells manipulated to constitutively express Mef2c demonstrated increased monopoiesis at the expense of granulopoiesis, whereas BM isolated from Mef2c(Delta/-) mice showed reduced levels of monocytic differentiation in response to cytokines. Mechanistic studies showed that loss of Mef2c expression correlated with reduced levels of transcripts encoding c-Jun, but not PU.1, C/EBPalpha, or JunB transcription factors. Inhibiting Jun expression by short-interfering RNA impaired Mef2c-mediated inhibition of granulocyte development. Moreover, retroviral expression of c-Jun in BM cells promoted monocytic differentiation. The ability of Mef2c to modulate cell-fate decisions between monocyte and granulocyte differentiation, coupled with its functional sensitivity to extracellular stimuli, demonstrate an important role in immunity--and, consistent with findings of other myeloid transcription factors, a target of oncogenic lesions in AML.
AB - Mef2c is a MADS (MCM1-agamous-deficient serum response factor) transcription factor best known for its role in muscle and cardiovascular development. A causal role of up-regulated MEF2C expression in myelomonocytic acute myeloid leukemia (AML) has recently been demonstrated. Due to the pronounced monocytic component observed in Mef2c-induced AML, this study was designed to assess the importance of Mef2c in normal myeloid differentiation. Analysis of bone marrow (BM) cells manipulated to constitutively express Mef2c demonstrated increased monopoiesis at the expense of granulopoiesis, whereas BM isolated from Mef2c(Delta/-) mice showed reduced levels of monocytic differentiation in response to cytokines. Mechanistic studies showed that loss of Mef2c expression correlated with reduced levels of transcripts encoding c-Jun, but not PU.1, C/EBPalpha, or JunB transcription factors. Inhibiting Jun expression by short-interfering RNA impaired Mef2c-mediated inhibition of granulocyte development. Moreover, retroviral expression of c-Jun in BM cells promoted monocytic differentiation. The ability of Mef2c to modulate cell-fate decisions between monocyte and granulocyte differentiation, coupled with its functional sensitivity to extracellular stimuli, demonstrate an important role in immunity--and, consistent with findings of other myeloid transcription factors, a target of oncogenic lesions in AML.
M3 - SCORING: Zeitschriftenaufsatz
VL - 111
SP - 4532
EP - 4541
JO - BLOOD
JF - BLOOD
SN - 0006-4971
IS - 9
M1 - 9
ER -
