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Eric N. Olson - One of the best experts on this subject based on the ideXlab platform.
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neuronal myocyte specific enhancer factor 2d Mef2d is required for normal circadian and sleep behavior in mice
The Journal of Neuroscience, 2019Co-Authors: Jennifer A Mohawk, Makito Sato, Eric N. Olson, Joseph S. TakahashiAbstract:The transcription factor, myocyte enhancer factor-2 (Mef2), is required for normal circadian behavior in Drosophila; however, its role in the mammalian circadian system has not been established. Of the four mammalian Mef2 genes, Mef2d is highly expressed in the suprachiasmatic nucleus (SCN) of the hypothalamus, a region critical for coordinating peripheral circadian clocks. Utilizing both conventional and brain-specific Mef2d knockout (Mef2d-/-) mouse lines, we demonstrate that Mef2D is essential for maintaining the length of the circadian free-running period of locomotor activity and normal sleep patterns in male mice. Crossing Mef2d-/- with Per2::luc reporter mice, we show that these behavioral changes are achieved without altering the endogenous period of the master circadian oscillator in the SCN. Together, our data suggest that alterations in behavior in Mef2d-/- mice may be the result of an effect on SCN output, rather than an effect on timekeeping within the SCN itself. These findings add to the growing body of evidence that Mef2 proteins play important roles in the brain. SIGNIFICANCE STATEMENT These studies are the first to show a role for Mef2 proteins in the brain outside of the hippocampus, and our findings suggest that these proteins may play diverse roles in the central nervous system. It is important to continue to build on our understanding of the roles of proteins acting in the SCN, because SCN dysfunction underlies jet lag in humans and influences the response to shift work schedules, which are now known as risk factors for the development of cancer. Our work on Mef2D could be the basis for opening new lines of research in the development and regulation of circadian rhythms.
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In Vivo Analysis of Mef2 Transcription Factors in Synapse Regulation and Neuronal Survival
2016Co-Authors: Waseem M. Akhtar, James A Richardson, Eric N. Olson, Ege T. Kavalali, Mi-sung Kim, Megumi Adachi, Michael J. Morris, Rhonda Bassel-duby, Lisa M. MonteggiaAbstract:Mef2 (A–D) transcription factors govern development, differentiation and maintenance of various cell types including neurons. The role of Mef2 isoforms in the brain has been studied using in vitro manipulations with only Mef2C examined in vivo. In order to understand specific as well as redundant roles of the Mef2 isoforms, we generated brain-specific deletion of Mef2A and found that Mef2aKO mice show normal behavior in a range of paradigms including learning and memory. We next generated Mef2a and Mef2d brain-specific double KO (Mef2a/dDKO) mice and observed deficits in motor coordination and enhanced hippocampal short-term synaptic plasticity, however there were no alterations in learning and memory, Schaffer collateral pathway long-term potentiation, or the number of dendritic spines. Since previous work has established a critical role for Mef2C in hippocampal plasticity, we generated a Mef2a, Mef2c and Mef2d brain-specific triple KO (Mef2a/c/ dTKO). Mef2a/c/d TKO mice have early postnatal lethality with increased neuronal apoptosis, indicative of a redundant role for the Mef2 factors in neuronal survival. We examined synaptic plasticity in the intact neurons in the Mef2a/c/d TKO mice and found significant impairments in short-term synaptic plasticity suggesting that Mef2C is the major isoform involved in hippocampal synaptic function. Collectively, these data highlight the key in vivo role of Mef2C isoform in the brain an
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requirement of Mef2a c and d for skeletal muscle regeneration
Proceedings of the National Academy of Sciences of the United States of America, 2014Co-Authors: Ning Liu, John M Shelton, James A Richardson, Rhonda S Basselduby, Benjamin R Nelson, Svetlana Bezprozvannaya, Eric N. OlsonAbstract:Regeneration of adult skeletal muscle following injury occurs through the activation of satellite cells, an injury-sensitive muscle stem cell population that proliferates, differentiates, and fuses with injured myofibers. Members of the myocyte enhancer factor 2 (Mef2) family of transcription factors play essential roles in muscle differentiation during embryogenesis, but their potential contributions to adult muscle regeneration have not been systematically explored. To investigate the potential involvement of Mef2 factors in muscle regeneration, we conditionally deleted the Mef2a, c, and d genes, singly and in combination, within satellite cells in mice, using tamoxifen-inducible Cre recombinase under control of the satellite cell-specific Pax7 promoter. We show that deletion of individual Mef2 genes has no effect on muscle regeneration in response to cardiotoxin injury. However, combined deletion of the Mef2a, c, and d genes results in a blockade to regeneration. Satellite cell-derived myoblasts lacking Mef2A, C, and D proliferate normally in culture, but cannot differentiate. The absence of Mef2A, C, and D in satellite cells is associated with aberrant expression of a broad collection of known and unique protein-coding and long noncoding RNA genes. These findings reveal essential and redundant roles of Mef2A, C, and D in satellite cell differentiation and identify a Mef2-dependent transcriptome associated with skeletal muscle regeneration.
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the Mef2d transcription factor mediates stress dependent cardiac remodeling in mice
Journal of Clinical Investigation, 2008Co-Authors: Dillon Phan, Eva Van Rooij, Joseph A. Hill, Xiaoxia Qi, John Mcanally, James A Richardson, Rhonda S Basselduby, Eric N. OlsonAbstract:The adult heart responds to excessive neurohumoral signaling and workload by a pathological growth response characterized by hypertrophy of cardiomyocytes and activation of a fetal program of cardiac gene expression. These responses culminate in diminished pump function, ventricular dilatation, wall thinning, and fibrosis, and can result in sudden death. Myocyte enhancer factor–2 (Mef2) transcription factors serve as targets of the signaling pathways that drive pathological cardiac remodeling, but the requirement for Mef2 factors in the progression of heart disease in vivo has not been determined. Mef2A and Mef2D are the primary Mef2 factors expressed in the adult heart. To specifically determine the role of Mef2D in pathological cardiac remodeling, we generated mice with a conditional Mef2D allele. Mef2D-null mice were viable, but were resistant to cardiac hypertrophy, fetal gene activation, and fibrosis in response to pressure overload and β-chronic adrenergic stimulation. Furthermore, we show in a transgenic mouse model that forced overexpression of Mef2D was sufficient to drive the fetal gene program and pathological remodeling of the heart. These results reveal a unique and important function for Mef2D in stress-dependent cardiac growth and reprogramming of gene expression in the adult heart.
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Regulation of skeletal muscle sarcomere integrity and postnatal muscle function by Mef2c.
Molecular and cellular biology, 2007Co-Authors: Matthew J. Potthoff, John Mcanally, James A Richardson, Michael A Arnold, Rhonda S Bassel-duby, Eric N. OlsonAbstract:Myocyte enhancer factor 2 (Mef2) transcription factors cooperate with the MyoD family of basic helix-loop-helix (bHLH) transcription factors to drive skeletal muscle development during embryogenesis, but little is known about the potential functions of Mef2 factors in postnatal skeletal muscle. Here we show that skeletal muscle-specific deletion of Mef2c in mice results in disorganized myofibers and perinatal lethality. In contrast, neither Mef2a nor Mef2d is required for normal skeletal muscle development in vivo. Skeletal muscle deficient in Mef2c differentiates and forms normal myofibers during embryogenesis, but myofibers rapidly deteriorate after birth due to disorganized sarcomeres and a loss of integrity of the M line. Microarray analysis of Mef2c null muscles identified several muscle structural genes that depend on Mef2C, including those encoding the M-line-specific proteins myomesin and M protein. We show that Mef2C directly regulates myomesin gene transcription and that loss of Mef2c in skeletal muscle results in improper sarcomere organization. These results reveal a key role for Mef2c in maintenance of sarcomere integrity and postnatal maturation of skeletal muscle.
Stephen P Hunger - One of the best experts on this subject based on the ideXlab platform.
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cloning and functional characterization of Mef2d dazap1 and dazap1 Mef2d fusion proteins created by a variant t 1 19 q23 p13 3 in acute lymphoblastic leukemia
Leukemia, 2005Co-Authors: Victor Prima, Lia Gore, Aimee Caires, Theresa Boomer, Miyako Yoshinari, Marileila Varellagarcia, M. Imaizumi, Stephen P HungerAbstract:We analyzed the TS-2 acute lymphoblastic leukemia (ALL) cell line that contains a t(1;19)(q23;p13.3) but lacks E2A-PBX1 fusion typically present in leukemias with this translocation. We found that the t(1;19) in TS-2 fuses the 19p13 gene DAZAP1 (Deleted in Azoospermia-Associated Protein 1) to the 1q23 gene Mef2D (Myocyte Enhancer Factor 2D), leading to expression of reciprocal in-frame DAZAP1/Mef2D and Mef2D/DAZAP1 transcripts. Mef2D is a member of the Mef2 family of DNA binding proteins that activate transcription of genes involved in control of muscle cell differentiation, and signaling pathways that mediate response to mitogenic signals and survival of neurons and T-lymphocytes. DAZAP1 is a novel RNA binding protein expressed most abundantly in the testis. We demonstrate that Mef2D/DAZAP1 binds avidly and specifically to DNA in a manner indistinguishable from that of native Mef2D and is a substantially more potent transcriptional activator than Mef2D. We also show that DAZAP1/Mef2D is a sequence-specific RNA-binding protein. Mef2D has been identified as a candidate oncogene in murine retroviral insertional mutagenesis studies. Our data implicate Mef2D in human cancer and suggest that Mef2D/DAZAP1 and/or DAZAP1/Mef2D contribute to leukemogenesis by altering signaling pathways normally regulated by wild-type Mef2D and DAZAP1.
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chimeric Mef2d and dazap1 fusion proteins are created by a variant t 1 19 q23 p13 3 in acute lymphoblastic leukemia all
Blood, 2004Co-Authors: Victor Prima, Lia Gore, Aimee Caires, Theresa Boomer, Miyako Yoshinari, Imaizume Masue, Varellagarcia Marileila, Stephen P HungerAbstract:The t(1;19)(q23;p13) is one of the most common chromosome translocations in ALL. In 90–95% of ALL cases with a t(1;19), the 19p13.3 gene E2A is fused to PBX1 located at 1q23, producing E2A-PBX1 chimeric proteins that possess transforming properties. The molecular abnormalities present in the 5–10% of ALL cases with a t(1;19) but no E2A-PBX1 fusion are unknown. TS-2 is an ALL cell line with a t(1;19)(q23;p13.3) but no E2A-PBX1 fusion. We used fluoresence in situ hybridization to localize the chromosome 19 breakpoint in TS-2 to a region approximately 400 kilobases telomeric to E2A and found that the t(1;19) in TS-2 fuses the 19p13 gene DAZAP1 (deleted in azoospermia associated protein 1) to the 1q23 gene Mef2D (myocte enhancer factor 2D). We cloned and sequenced the fusion genes and found they encode for reciprocal in-frame DAZAP1/Mef2D and Mef2D/DAZAP1 fusion transcripts, both of which are expressed in TS-2. Mef2D is a member of the Mef2 family of DNA binding proteins, which were originally characterized as muscle-specific transcription factors that regulated transcription of genes involved in myogenic differentiation. Mef2 proteins are now recognized to have more diverse functions: they are transcriptional effectors of mitogenic signaling pathways and inflammation, play critical roles in calcium-regulated signaling pathways that mediate survival of neurons and T-lympocytes, and participate in neuronal plasticity. DAZAP1 is a protein with novel RNA binding properties that is expressed most abundantly in testis and to a lesser extent in thymus. Mef2D-DAZAP1 includes the Mef2D MADS (MCM1, agamous, deficiens, and serum response factor) box and adjacent Mef2D domain that mediate sequence-specific DNA binding and protein-protein interactions, as well as one of two Mef2D transcriptional activation domains (TAD) fused to the C-terminus of DAZAP1. The DAZAP1-Mef2D chimera includes an intact first and truncated second RNA recognition motif from DAZAP1 joined to the C-terminus of Mef2D that includes its second TAD. We performed electrophoretic mobility shift assays using cognate and mutant Mef2D DNA recognition sites and found that Mef2D/DAZAP1 binds avidly and specifically to DNA in a manner indistinguishable from that of native Mef2D. We found that Mef2D/DAZAP1 activated transcription of a luciferase reporter gene under control of Mef2D recognition elements with substantially more potency than did wild type Mef2D. We also show that DAZAP1/Mef2D proteins bind RNA in a sequence specific manner analogous to that of wild type DAZAP1. Mef2D has been identified as a candidate oncogene involved in development of leukemia/lymphoma via murine retroviral insertional mutagenesis studies. Our data implicate Mef2D in human cancer and suggest that Mef2D/DAZAP1 and/or DAZAP1/Mef2D contributes to leukemogenesis by altering signaling pathways normally regulated by wild type Mef2D and DAZAP1.
Yingchao Zhao - One of the best experts on this subject based on the ideXlab platform.
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Mef2d wnt β catenin pathway regulates the proliferation of gastric cancer cells and is regulated by microrna 19
Tumor Biology, 2016Co-Authors: Kai Xu, Yingchao ZhaoAbstract:The underlying molecular pathogenesis in gastric cancer remains poorly unknown. The transcription factor myocyte enhancer factor 2D (Mef2D) participates in the initiation and development of many human cancers. However, its potential roles in gastric cancer have surprisingly not been studied. In present study, we first explored Mef2’s expression in gastric cancer, finding that only Mef2D rather than Mef2A, 2B, or 2C was elevated in gastric cancer clinical specimens. Furthermore, immunohistochemical analysis on the tissue samples obtained from 260 patients with gastric cancer revealed that Mef2D expression was significantly associated with the clinical stage, vascular invasion, metastasis, and tumor size. Gastric cancer patients with Mef2D expression showed a significantly shorter overall survival time compared with that of patients lacking of Mef2D. Multivariate analysis revealed that Mef2D expression was an independent prognostic factor for overall survival. These results indicated that Mef2D was a prognostic marker for gastric cancer. Notably, Mef2D silencing was able to reduce the proliferation and survival of gastric cancer cells. Further study revealed that Mef2D suppression significantly inactivated the oncogenic Wnt/β-catenin pathway. Downregulation of Mef2D inhibited the tumorigenesis of gastric cancer cells in nude mice. Finally, Mef2D is a direct target of miR-19, which was found to be decreased in gastric cancer clinical specimens. Collectively, we found that miR-19/Mef2D/Wnt/β-catenin regulatory network contributes to the growth of gastric cancer, hinting a new promising target for gastric cancer treatment.
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Mef2d wnt β catenin pathway regulates the proliferation of gastric cancer cells and is regulated by microrna 19
Tumor Biology, 2016Co-Authors: Kai Xu, Yingchao ZhaoAbstract:The underlying molecular pathogenesis in gastric cancer remains poorly unknown. The transcription factor myocyte enhancer factor 2D (Mef2D) participates in the initiation and development of many human cancers. However, its potential roles in gastric cancer have surprisingly not been studied. In present study, we first explored Mef2’s expression in gastric cancer, finding that only Mef2D rather than Mef2A, 2B, or 2C was elevated in gastric cancer clinical specimens. Furthermore, immunohistochemical analysis on the tissue samples obtained from 260 patients with gastric cancer revealed that Mef2D expression was significantly associated with the clinical stage, vascular invasion, metastasis, and tumor size. Gastric cancer patients with Mef2D expression showed a significantly shorter overall survival time compared with that of patients lacking of Mef2D. Multivariate analysis revealed that Mef2D expression was an independent prognostic factor for overall survival. These results indicated that Mef2D was a prognostic marker for gastric cancer. Notably, Mef2D silencing was able to reduce the proliferation and survival of gastric cancer cells. Further study revealed that Mef2D suppression significantly inactivated the oncogenic Wnt/β-catenin pathway. Downregulation of Mef2D inhibited the tumorigenesis of gastric cancer cells in nude mice. Finally, Mef2D is a direct target of miR-19, which was found to be decreased in gastric cancer clinical specimens. Collectively, we found that miR-19/Mef2D/Wnt/β-catenin regulatory network contributes to the growth of gastric cancer, hinting a new promising target for gastric cancer treatment.
Milena M Andzelm - One of the best experts on this subject based on the ideXlab platform.
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a late phase of long term synaptic depression in cerebellar purkinje cells requires activation of Mef2
Cell Reports, 2019Co-Authors: Milena M Andzelm, Devorah Vanness, Michael E Greenberg, David J LindenAbstract:Summary The Mef2 family of transcription factors restricts excitatory synapse number in an activity-dependent fashion during development, yet Mef2 has not been implicated in long-term synaptic depression (LTD), which is thought to initiate synapse elimination. Mutations in Mef2 pathways are implicated in autism spectrum disorders, which include cerebellar dysfunction. Here, we test the hypothesis that cerebellar LTD requires postsynaptic activation of Mef2. Knockdown of Mef2D produces suppression of the transcription-dependent late phase of LTD in cultured Purkinje cells. The late phase of LTD is also completely blocked in Purkinje cells derived from Mef2A+Mef2D null mice and rescued with plasmids that drive expression of Mef2D but not phosphatase-resistant mutant Mef2D S444D. Wild-type Purkinje cells transfected with a constitutively active form of Mef2 show no alterations of synaptic strength. Thus, postsynaptic activation of Mef2 by S444 dephosphorylation is necessary, but not sufficient, for the late phase of cerebellar LTD.
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A Late Phase of Long-Term Synaptic Depression in Cerebellar Purkinje Cells Requires Activation of Mef2
Elsevier, 2019Co-Authors: Milena M Andzelm, Devorah Vanness, Michael E Greenberg, David J LindenAbstract:Summary: The Mef2 family of transcription factors restricts excitatory synapse number in an activity-dependent fashion during development, yet Mef2 has not been implicated in long-term synaptic depression (LTD), which is thought to initiate synapse elimination. Mutations in Mef2 pathways are implicated in autism spectrum disorders, which include cerebellar dysfunction. Here, we test the hypothesis that cerebellar LTD requires postsynaptic activation of Mef2. Knockdown of Mef2D produces suppression of the transcription-dependent late phase of LTD in cultured Purkinje cells. The late phase of LTD is also completely blocked in Purkinje cells derived from Mef2A+Mef2D null mice and rescued with plasmids that drive expression of Mef2D but not phosphatase-resistant mutant Mef2D S444D. Wild-type Purkinje cells transfected with a constitutively active form of Mef2 show no alterations of synaptic strength. Thus, postsynaptic activation of Mef2 by S444 dephosphorylation is necessary, but not sufficient, for the late phase of cerebellar LTD. : Neurodevelopmental disorders can reflect defects in synaptic pruning, which is thought to require activity-dependent weakening of synapses, a process called long-term depression. Andzelm et al. show that Mef2, which is important for neuronal development, is required for the late phase of long-term depression in the cerebellum. Keywords: Arc, MRE, cerebellum, motor learning, memory, autis
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Mef2d drives photoreceptor development through a genome wide competition for tissue specific enhancers
Neuron, 2015Co-Authors: Milena M Andzelm, Timothy J Cherry, David A Harmin, Annabel C Boeke, Martin Hemberg, Basil S Pawlyk, Michael A Sandberg, Steven W Flavell, Athar N Malik, Elio RaviolaAbstract:Summary Organismal development requires the precise coordination of genetic programs to regulate cell fate and function. Mef2 transcription factors (TFs) play essential roles in this process but how these broadly expressed factors contribute to the generation of specific cell types during development is poorly understood. Here we show that despite being expressed in virtually all mammalian tissues, in the retina Mef2D binds to retina-specific enhancers and controls photoreceptor cell development. Mef2D achieves specificity by cooperating with a retina-specific factor CRX, which recruits Mef2D away from canonical Mef2 binding sites and redirects it to retina-specific enhancers that lack the consensus Mef2-binding sequence. Once bound to retina-specific enhancers, Mef2D and CRX co-activate the expression of photoreceptor-specific genes that are critical for retinal function. These findings demonstrate that broadly expressed TFs acquire specific functions through competitive recruitment to enhancers by tissue-specific TFs and through selective activation of these enhancers to regulate tissue-specific genes.
Victor Prima - One of the best experts on this subject based on the ideXlab platform.
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cloning and functional characterization of Mef2d dazap1 and dazap1 Mef2d fusion proteins created by a variant t 1 19 q23 p13 3 in acute lymphoblastic leukemia
Leukemia, 2005Co-Authors: Victor Prima, Lia Gore, Aimee Caires, Theresa Boomer, Miyako Yoshinari, Marileila Varellagarcia, M. Imaizumi, Stephen P HungerAbstract:We analyzed the TS-2 acute lymphoblastic leukemia (ALL) cell line that contains a t(1;19)(q23;p13.3) but lacks E2A-PBX1 fusion typically present in leukemias with this translocation. We found that the t(1;19) in TS-2 fuses the 19p13 gene DAZAP1 (Deleted in Azoospermia-Associated Protein 1) to the 1q23 gene Mef2D (Myocyte Enhancer Factor 2D), leading to expression of reciprocal in-frame DAZAP1/Mef2D and Mef2D/DAZAP1 transcripts. Mef2D is a member of the Mef2 family of DNA binding proteins that activate transcription of genes involved in control of muscle cell differentiation, and signaling pathways that mediate response to mitogenic signals and survival of neurons and T-lymphocytes. DAZAP1 is a novel RNA binding protein expressed most abundantly in the testis. We demonstrate that Mef2D/DAZAP1 binds avidly and specifically to DNA in a manner indistinguishable from that of native Mef2D and is a substantially more potent transcriptional activator than Mef2D. We also show that DAZAP1/Mef2D is a sequence-specific RNA-binding protein. Mef2D has been identified as a candidate oncogene in murine retroviral insertional mutagenesis studies. Our data implicate Mef2D in human cancer and suggest that Mef2D/DAZAP1 and/or DAZAP1/Mef2D contribute to leukemogenesis by altering signaling pathways normally regulated by wild-type Mef2D and DAZAP1.
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chimeric Mef2d and dazap1 fusion proteins are created by a variant t 1 19 q23 p13 3 in acute lymphoblastic leukemia all
Blood, 2004Co-Authors: Victor Prima, Lia Gore, Aimee Caires, Theresa Boomer, Miyako Yoshinari, Imaizume Masue, Varellagarcia Marileila, Stephen P HungerAbstract:The t(1;19)(q23;p13) is one of the most common chromosome translocations in ALL. In 90–95% of ALL cases with a t(1;19), the 19p13.3 gene E2A is fused to PBX1 located at 1q23, producing E2A-PBX1 chimeric proteins that possess transforming properties. The molecular abnormalities present in the 5–10% of ALL cases with a t(1;19) but no E2A-PBX1 fusion are unknown. TS-2 is an ALL cell line with a t(1;19)(q23;p13.3) but no E2A-PBX1 fusion. We used fluoresence in situ hybridization to localize the chromosome 19 breakpoint in TS-2 to a region approximately 400 kilobases telomeric to E2A and found that the t(1;19) in TS-2 fuses the 19p13 gene DAZAP1 (deleted in azoospermia associated protein 1) to the 1q23 gene Mef2D (myocte enhancer factor 2D). We cloned and sequenced the fusion genes and found they encode for reciprocal in-frame DAZAP1/Mef2D and Mef2D/DAZAP1 fusion transcripts, both of which are expressed in TS-2. Mef2D is a member of the Mef2 family of DNA binding proteins, which were originally characterized as muscle-specific transcription factors that regulated transcription of genes involved in myogenic differentiation. Mef2 proteins are now recognized to have more diverse functions: they are transcriptional effectors of mitogenic signaling pathways and inflammation, play critical roles in calcium-regulated signaling pathways that mediate survival of neurons and T-lympocytes, and participate in neuronal plasticity. DAZAP1 is a protein with novel RNA binding properties that is expressed most abundantly in testis and to a lesser extent in thymus. Mef2D-DAZAP1 includes the Mef2D MADS (MCM1, agamous, deficiens, and serum response factor) box and adjacent Mef2D domain that mediate sequence-specific DNA binding and protein-protein interactions, as well as one of two Mef2D transcriptional activation domains (TAD) fused to the C-terminus of DAZAP1. The DAZAP1-Mef2D chimera includes an intact first and truncated second RNA recognition motif from DAZAP1 joined to the C-terminus of Mef2D that includes its second TAD. We performed electrophoretic mobility shift assays using cognate and mutant Mef2D DNA recognition sites and found that Mef2D/DAZAP1 binds avidly and specifically to DNA in a manner indistinguishable from that of native Mef2D. We found that Mef2D/DAZAP1 activated transcription of a luciferase reporter gene under control of Mef2D recognition elements with substantially more potency than did wild type Mef2D. We also show that DAZAP1/Mef2D proteins bind RNA in a sequence specific manner analogous to that of wild type DAZAP1. Mef2D has been identified as a candidate oncogene involved in development of leukemia/lymphoma via murine retroviral insertional mutagenesis studies. Our data implicate Mef2D in human cancer and suggest that Mef2D/DAZAP1 and/or DAZAP1/Mef2D contributes to leukemogenesis by altering signaling pathways normally regulated by wild type Mef2D and DAZAP1.