Ca2+-dependent Gene Expression Mediated by MEF2 Transcription Factors

Blaeser, Frank; Ho, Nga; Prywes, Ron; Chatila, Talal A.

doi:10.1074/jbc.275.1.197

Cited by 186 publications

(171 citation statements)

References 56 publications

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“…3) [72]. As in other systems, MEF2-dependent transcription in T cells is activated by Ca 2þ signals and by ectopic expression of activated CaMK IV, calcineurin, or ERK5/BMK1 [73][74][75].…”

Section: Biological Roles Of Class Iia Hdacsmentioning

confidence: 92%

Class II histone deacetylases: versatile regulators

2003

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Histone acetylation and deacetylation play essential roles in modifying chromatin structure and regulating gene expression in eukaryotes. Histone deacetylases (HDACs) catalyze the deacetylation of lysine residues in the histone N-terminal tails and are found in large multiprotein complexes with transcriptional co-repressors. Human HDACs are grouped into three classes based on their similarity to known yeast factors: class I HDACs are similar to the yeast transcriptional repressor yRPD3, class II HDACs to yHDA1 and class III HDACs to ySIR2. In this review, we focus on the biology of class II HDACs. These newly discovered enzymes have been implicated as global regulators of gene expression during cell differentiation and development. We discuss their emerging biological functions and the molecular mechanisms by which they are regulated.

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Section: Biological Roles Of Class Iia Hdacsmentioning

confidence: 92%

Class II histone deacetylases: versatile regulators

2003

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“…(ii) Binding of calcineurin-activated NF-AT to MEF2D. NF-AT, a well-known calcineurin substrate in non-activated T cells, translocates from the cytosol into the nucleus where it forms a ternary complex with MEF2 and p300, leading to full activation of Nur77 expression (Blaeser et al, 2000;Youn et al, 2000a).…”

Section: Menin Represses Jund Transcriptional Activity In Protein Kinmentioning

confidence: 99%

Menin represses JunD transcriptional activity in protein kinase Cθ-mediated Nur77 expression

Kim¹,

Lee²,

Kim³

et al. 2005

Exp Mol Med

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TCR signaling leading to thymocyte apoptosis is mediated through the expression of the Nur77 family of orphan nuclear receptors. It has been shown that the Nur77 promoter is activated by at least two signaling pathways, one mediated by calcium and the other by protein kinase C (PKC). MEF2D has been known to regulate Nur77 expression in a calciumdependent manner. The mechanism by which calcium regulates MEF2D is through dissociation of calcium-sensitive MEF2 corepressors (Cabin1/ HDACs, HDAC4/5) and the association with calcineurin-activated transcription factor NF-AT and the coactivator p300. However, little is known about how PKC activates the Nur77 promoter. Herein, we report that PKC targets AP-1 like response element in the Nur77 promoter where JunD constitutively binds. PKCθ triggers mitogen-activated protein kinaseinediated phosphorylation of JunD, and increases transcriptional activity of JunD, cooperatively with p300. Menin is identified as the transcriptional corepressor for JunD via recruitment of mSin3-istone deacetylases. In fact, Menin represses PKCθ/ p300-mediated transcriptional activity of JunD in T cell. Its dynamic regulation of histone modifiers with JunD is responsible for PKCθ-synergistic effect on Nur77 expression in T cell.

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“…Mitogen-activated protein kinases stimulate MEF2 transcriptional activity through phosphorylation of the MEF2 transactivation domain (11,12). The calcium͞calmodu-lin-dependent phosphatase calcineurin activates MEF2 by a posttranslational mechanism that may require association of MEF2 with the nuclear factor of activated T cells transcription factor (13)(14)(15)(16). Recently, we reported that calcium͞calmodulin-dependent protein kinase (CaMK) signaling stimulates MEF2 activity by disrupting MEF2-HDAC complexes, with resulting export of HDAC5 from the nucleus to the cytoplasm (10,17).…”

mentioning

confidence: 99%

Activation of the myocyte enhancer factor-2 transcription factor by calcium/calmodulin-dependent protein kinase-stimulated binding of 14-3-3 to histone deacetylase 5

McKinsey

Zhang

Olson

2000

Proc. Natl. Acad. Sci. U.S.A.

461

426

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Skeletal muscle differentiation is controlled by interactions between myocyte enhancer factor-2 (MEF2) and myogenic basic helix-loop-helix transcription factors. Association of MEF2 with histone deacetylases (HDAC) -4 and -5 results in repression of MEF2 target genes and inhibition of myogenesis. Calcium͞calmodulin-dependent protein kinase (CaMK) signaling promotes myogenesis by disrupting MEF2-HDAC complexes and stimulating HDAC nuclear export. To further define the mechanisms that confer CaMK responsiveness to HDAC4 and -5, we performed yeast two-hybrid screens to identify HDAC-interacting factors. These screens revealed interactions between HDAC4 and members of the 14-3-3 family of proteins, which function as signal-dependent intracellular chaperones. HDAC4 binds constitutively to 14-3-3 in yeast and mammalian cells, whereas HDAC5 binding to 14-3-3 is largely dependent on CaMK signaling. CaMK phosphorylates serines -259 and -498 in HDAC5, which subsequently serve as docking sites for 14-3-3. Our studies suggest that 14-3-3 binding to HDAC5 is required for CaMK-dependent disruption of MEF2-HDAC complexes and nuclear export of HDAC5, and implicate 14-3-3 as a signal-dependent regulator of muscle cell differentiation.

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Ca2+-dependent Gene Expression Mediated by MEF2 Transcription Factors

Cited by 186 publications

References 56 publications

Class II histone deacetylases: versatile regulators

Class II histone deacetylases: versatile regulators

Menin represses JunD transcriptional activity in protein kinase Cθ-mediated Nur77 expression

Activation of the myocyte enhancer factor-2 transcription factor by calcium/calmodulin-dependent protein kinase-stimulated binding of 14-3-3 to histone deacetylase 5

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