Gene Symbol: Hdac4
Description: histone deacetylase 4
Alias: 4932408F19Rik, HD4, histone deacetylase 4
Species: mouse
Products:     Hdac4

Top Publications

  1. Heverin M, Meaney S, Brafman A, Shafir M, Olin M, Shafaati M, et al. Studies on the cholesterol-free mouse: strong activation of LXR-regulated hepatic genes when replacing cholesterol with desmosterol. Arterioscler Thromb Vasc Biol. 2007;27:2191-7 pubmed
    ..Characterization of cholesterol homeostasis in male mice with a genetic inactivation of 3beta-hydroxysteroid-delta24-reductase, causing replacement of almost all cholesterol with desmosterol...
  2. Evankovich J, Cho S, Zhang R, Cardinal J, Dhupar R, Zhang L, et al. High mobility group box 1 release from hepatocytes during ischemia and reperfusion injury is mediated by decreased histone deacetylase activity. J Biol Chem. 2010;285:39888-97 pubmed publisher
    ..We identified the isoforms HDAC1 and HDAC4 as critical in regulating acetylated HMGB1 release...
  3. Winbanks C, Wang B, Beyer C, Koh P, White L, Kantharidis P, et al. TGF-beta regulates miR-206 and miR-29 to control myogenic differentiation through regulation of HDAC4. J Biol Chem. 2011;286:13805-14 pubmed publisher
    ..We further demonstrate that TGF-? treatment of myogenic cells is associated with increased expression of histone deacetylase 4 (HDAC4), a key inhibitor of muscle differentiation that has been identified as a target for regulation by ..
  4. Chang S, McKinsey T, Zhang C, Richardson J, Hill J, Olson E. Histone deacetylases 5 and 9 govern responsiveness of the heart to a subset of stress signals and play redundant roles in heart development. Mol Cell Biol. 2004;24:8467-76 pubmed
    ..These findings reveal central roles for HDACs 5 and 9 in the suppression of a subset of cardiac stress signals as well as redundant functions in the control of cardiac development. ..
  5. Potthoff M, Wu H, Arnold M, Shelton J, Backs J, McAnally J, et al. Histone deacetylase degradation and MEF2 activation promote the formation of slow-twitch myofibers. J Clin Invest. 2007;117:2459-67 pubmed
    ..These findings provide what we believe are new insights into the molecular basis of skeletal muscle function and have important implications for possible therapeutic interventions into muscular diseases. ..
  6. Li J, Chen J, Ricupero C, Hart R, Schwartz M, Kusnecov A, et al. Nuclear accumulation of HDAC4 in ATM deficiency promotes neurodegeneration in ataxia telangiectasia. Nat Med. 2012;18:783-90 pubmed publisher
    ..Here we report that ataxia telangiectasia mutated (ATM) deficiency causes nuclear accumulation of histone deacetylase 4 (HDAC4) in neurons and promotes neurodegeneration...
  7. Wilson A, Byun D, Nasser S, Murray L, Ayyanar K, Arango D, et al. HDAC4 promotes growth of colon cancer cells via repression of p21. Mol Biol Cell. 2008;19:4062-75 pubmed publisher
    The class II Histone deacetylase (HDAC), HDAC4, is expressed in a tissue-specific manner, and it represses differentiation of specific cell types...
  8. Backs J, Backs T, Bezprozvannaya S, McKinsey T, Olson E. Histone deacetylase 5 acquires calcium/calmodulin-dependent kinase II responsiveness by oligomerization with histone deacetylase 4. Mol Cell Biol. 2008;28:3437-45 pubmed publisher
    Calcium/calmodulin-dependent protein kinase II (CaMKII) phosphorylates histone deacetylase 4 (HDAC4), a class IIa HDAC, resulting in the cytosolic accumulation of HDAC4 and the derepression of the transcription factor myocyte enhancer ..
  9. Cernotta N, Clocchiatti A, Florean C, Brancolini C. Ubiquitin-dependent degradation of HDAC4, a new regulator of random cell motility. Mol Biol Cell. 2011;22:278-89 pubmed publisher
    HDAC4 (histone deacetylase 4) belongs to class IIa of histone deacetylases, which groups important regulators of gene expression, controlling pleiotropic cellular functions...

More Information


  1. Tang H, MacPherson P, Marvin M, Meadows E, Klein W, Yang X, et al. A histone deacetylase 4/myogenin positive feedback loop coordinates denervation-dependent gene induction and suppression. Mol Biol Cell. 2009;20:1120-31 pubmed publisher
    ..Recently, it was reported that histone deacetylase 4 (HDAC4) can mediate denervation-induced myogenin and nicotinic acetylcholine receptor gene expression...
  2. Kim M, Akhtar M, Adachi M, Mahgoub M, Bassel Duby R, Kavalali E, et al. An essential role for histone deacetylase 4 in synaptic plasticity and memory formation. J Neurosci. 2012;32:10879-86 pubmed publisher
    ..Here, we show that selective loss of Hdac4 in brain results in impairments in hippocampal-dependent learning and memory and long-term synaptic plasticity...
  3. Choi M, Cohen T, Barrientos T, Wang B, Li M, Simmons B, et al. A direct HDAC4-MAP kinase crosstalk activates muscle atrophy program. Mol Cell. 2012;47:122-32 pubmed publisher
    ..In denervated muscle, activation of the atrophy program requires HDAC4, a potent repressor of the master muscle transcription factor MEF2...
  4. Sailaja B, Cohen Carmon D, Zimmerman G, Soreq H, Meshorer E. Stress-induced epigenetic transcriptional memory of acetylcholinesterase by HDAC4. Proc Natl Acad Sci U S A. 2012;109:E3687-95 pubmed publisher
    ..H3K9 hypoacetylation was associated with a selective, sodium butyrate-reversible promoter accumulation of HDAC4. Hippocampal suppression of HDAC4 in vivo completely abolished the long-lasting AChE-related and behavioral stress ..
  5. Williams A, Valdez G, Moresi V, Qi X, McAnally J, Elliott J, et al. MicroRNA-206 delays ALS progression and promotes regeneration of neuromuscular synapses in mice. Science. 2009;326:1549-54 pubmed publisher
    ..miR-206 mediates these effects at least in part through histone deacetylase 4 and fibroblast growth factor signaling pathways...
  6. Gupta M, Samant S, Smith S, Shroff S. HDAC4 and PCAF bind to cardiac sarcomeres and play a role in regulating myofilament contractile activity. J Biol Chem. 2008;283:10135-46 pubmed publisher
    ..We found that a Class II HDAC, HDAC4, and an HAT, PCAF, associate with cardiac myofilaments...
  7. Price V, Wang L, D Mello S. Conditional deletion of histone deacetylase-4 in the central nervous system has no major effect on brain architecture or neuronal viability. J Neurosci Res. 2013;91:407-15 pubmed publisher
    ..from different laboratories using cell culture and in vivo model systems indicates that histone deacetylase-4 (HDAC4) plays an essential role in maintaining neuronal survival...
  8. Liu Y, Randall W, Schneider M. Activity-dependent and -independent nuclear fluxes of HDAC4 mediated by different kinases in adult skeletal muscle. J Cell Biol. 2005;168:887-97 pubmed
    ..Here, we show that repetitive slow fiber type electrical stimulation, but not fast fiber type stimulation, caused HDAC4-GFP, but not HDAC5-GFP, to translocate from the nucleus to the cytoplasm in cultured adult skeletal muscle fibers...
  9. Rajan I, Savelieva K, Ye G, Wang C, Malbari M, Friddle C, et al. Loss of the putative catalytic domain of HDAC4 leads to reduced thermal nociception and seizures while allowing normal bone development. PLoS ONE. 2009;4:e6612 pubmed publisher
    b>Histone deacetylase 4 (HDAC4) has been associated with muscle & bone development [1]-[6]. N-terminal MEF2 and RUNX2 binding domains of HDAC4 have been shown to mediate these effects in vitro...
  10. Chen B, Cepko C. HDAC4 regulates neuronal survival in normal and diseased retinas. Science. 2009;323:256-9 pubmed publisher
    b>Histone deacetylase 4 (HDAC4) shuttles between the nucleus and cytoplasm and serves as a nuclear co-repressor that regulates bone and muscle development...
  11. Lu J, McKinsey T, Nicol R, Olson E. Signal-dependent activation of the MEF2 transcription factor by dissociation from histone deacetylases. Proc Natl Acad Sci U S A. 2000;97:4070-5 pubmed
  12. Moresi V, Williams A, Meadows E, Flynn J, Potthoff M, McAnally J, et al. Myogenin and class II HDACs control neurogenic muscle atrophy by inducing E3 ubiquitin ligases. Cell. 2010;143:35-45 pubmed publisher
    ..Thus, myogenin plays a dual role as both a regulator of muscle development and an inducer of neurogenic atrophy. These findings reveal a specific pathway for muscle wasting and potential therapeutic targets for this disorder. ..
  13. Cohen T, Waddell D, Barrientos T, Lu Z, Feng G, Cox G, et al. The histone deacetylase HDAC4 connects neural activity to muscle transcriptional reprogramming. J Biol Chem. 2007;282:33752-9 pubmed
    ..Here we identify the histone deacetylase HDAC4 as the critical linker connecting neural activity to muscle transcription...
  14. Vega R, Matsuda K, Oh J, Barbosa A, Yang X, Meadows E, et al. Histone deacetylase 4 controls chondrocyte hypertrophy during skeletogenesis. Cell. 2004;119:555-66 pubmed
    ..Here we report that HDAC4, which is expressed in prehypertrophic chondrocytes, regulates chondrocyte hypertrophy and endochondral bone ..
  15. Ago T, Liu T, Zhai P, Chen W, Li H, Molkentin J, et al. A redox-dependent pathway for regulating class II HDACs and cardiac hypertrophy. Cell. 2008;133:978-93 pubmed publisher
    ..Both Cys-274/Cys-276 in DnaJb5 and Cys-667/Cys-669 in HDAC4 are oxidized and form intramolecular disulfide bonds in response to reactive oxygen species (ROS)-generating ..
  16. Wang A, Kruhlak M, Wu J, Bertos N, Vezmar M, Posner B, et al. Regulation of histone deacetylase 4 by binding of 14-3-3 proteins. Mol Cell Biol. 2000;20:6904-12 pubmed
    ..Here we describe results demonstrating that HDAC4, a member of class II human HDACs, is localized in the cytoplasm and/or the nucleus...
  17. Cohen T, Barrientos T, Hartman Z, Garvey S, Cox G, Yao T. The deacetylase HDAC4 controls myocyte enhancing factor-2-dependent structural gene expression in response to neural activity. FASEB J. 2009;23:99-106 pubmed publisher
    b>Histone deacetylase 4 (HDAC4) binds and inhibits activation of the critical muscle transcription factor myocyte enhancer factor-2 (MEF2)...
  18. Arnold M, Kim Y, Czubryt M, Phan D, McAnally J, Qi X, et al. MEF2C transcription factor controls chondrocyte hypertrophy and bone development. Dev Cell. 2007;12:377-89 pubmed
    ..Endochondral bone formation is exquisitely sensitive to the balance between MEF2C and the corepressor histone deacetylase 4 (HDAC4), such that bone deficiency of Mef2c mutant mice can be rescued by an Hdac4 mutation, and ectopic ..
  19. Sando R, Gounko N, Pieraut S, Liao L, Yates J, Maximov A. HDAC4 governs a transcriptional program essential for synaptic plasticity and memory. Cell. 2012;151:821-834 pubmed publisher
    ..However, the molecular basis of this process remains poorly understood. We found that HDAC4, a histone deacetylase that shuttles between the nucleus and cytoplasm, controls a transcriptional program ..
  20. Kozhemyakina E, Cohen T, Yao T, Lassar A. Parathyroid hormone-related peptide represses chondrocyte hypertrophy through a protein phosphatase 2A/histone deacetylase 4/MEF2 pathway. Mol Cell Biol. 2009;29:5751-62 pubmed publisher
    ..PTHrP/forskolin induces dephosphorylation of histone deacetylase 4 (HDAC4) phospho-S246, which decreases interaction of HDAC4 with cytoplasmic 14-3-3 proteins and promotes ..
  21. Darcy M, Calvin K, Cavnar K, Ouimet C. Regional and subcellular distribution of HDAC4 in mouse brain. J Comp Neurol. 2010;518:722-40 pubmed publisher
    ..Some HDACs, including HDAC4, shuttle between the cytoplasm and nucleus in response to physiological cues such as calcium signaling...
  22. Liu Y, Hernández Ochoa E, Randall W, Schneider M. NOX2-dependent ROS is required for HDAC5 nuclear efflux and contributes to HDAC4 nuclear efflux during intense repetitive activity of fast skeletal muscle fibers. Am J Physiol Cell Physiol. 2012;303:C334-47 pubmed publisher
    Reactive oxygen species (ROS) have been linked to oxidation and nuclear efflux of class IIa histone deacetylase 4 (HDAC4) in cardiac muscle...
  23. Cui H, Moore J, Ashimi S, Mason B, Drawbridge J, Han S, et al. Eating disorder predisposition is associated with ESRRA and HDAC4 mutations. J Clin Invest. 2013;123:4706-13 pubmed
    ..the second family, analysis of eight members across four generations identified a missense mutation in the histone deacetylase 4 (HDAC4) gene that segregated with illness...
  24. Martin M, Kettmann R, Dequiedt F. Class IIa histone deacetylases: conducting development and differentiation. Int J Dev Biol. 2009;53:291-301 pubmed publisher
    ..Elucidating cellular and molecular mechanisms by which functions of class IIa HDACs are modulated could potentially lead to new therapeutic opportunities for various diseases. ..
  25. Addis R, Prasad M, Yochem R, Zhan X, Sheets T, Axelman J, et al. OCT3/4 regulates transcription of histone deacetylase 4 (Hdac4) in mouse embryonic stem cells. J Cell Biochem. 2010;111:391-401 pubmed publisher
    ..One segment corresponds to a region within the first intron of the gene encoding histone deacetylase 4 (Hdac4), a Class II histone deacetylase...
  26. Lu W, You R, Yuan X, Yang T, Samuel E, Marcano D, et al. The microRNA miR-22 inhibits the histone deacetylase HDAC4 to promote T(H)17 cell-dependent emphysema. Nat Immunol. 2015;16:1185-94 pubmed publisher
    ..miR-22 controlled the activation of APCs and T(H)17 responses through the activation of AP-1 transcription factor complexes and the histone deacetylase HDAC4. Thus, miR-22 is a critical regulator of both emphysema and T(H)17 responses.
  27. Choi M, Ryu S, Hao R, Wang B, Kapur M, Fan C, et al. HDAC4 promotes Pax7-dependent satellite cell activation and muscle regeneration. EMBO Rep. 2014;15:1175-83 pubmed publisher
    ..Here, we identify HDAC4 as a regulator of Pax7-dependent muscle regeneration...
  28. Obri A, Makinistoglu M, Zhang H, Karsenty G. HDAC4 integrates PTH and sympathetic signaling in osteoblasts. J Cell Biol. 2014;205:771-80 pubmed publisher
    ..In this paper, we show that PTH favors Rankl expression by triggering the ubiquitination of HDAC4, a class II histone deacetylase, via Smurf2...
  29. Luan B, Goodarzi M, Phillips N, Guo X, Chen Y, Yao J, et al. Leptin-mediated increases in catecholamine signaling reduce adipose tissue inflammation via activation of macrophage HDAC4. Cell Metab. 2014;19:1058-65 pubmed publisher
    ..increases in cAMP signaling that reduce inflammatory gene expression via the activation of the histone deacetylase HDAC4. cAMP stimulates HDAC4 activity through the PKA-dependent inhibition of the salt-inducible kinases (SIKs), which ..
  30. Micheli L, D Andrea G, Leonardi L, Tirone F. HDAC1, HDAC4, and HDAC9 Bind to PC3/Tis21/Btg2 and Are Required for Its Inhibition of Cell Cycle Progression and Cyclin D1 Expression. J Cell Physiol. 2017;232:1696-1707 pubmed publisher
    ..Here, we report that PC3/Tis21 associates with HDAC1, HDAC4, and HDAC9 in vivo, in fibroblast cells...
  31. Kang Y, Kim J, Anderson J, Wu J, Gleim S, Kundu R, et al. Apelin-APJ signaling is a critical regulator of endothelial MEF2 activation in cardiovascular development. Circ Res. 2013;113:22-31 pubmed publisher
    ..Apj-/- mice have greater endocardial Hdac4 and Hdac5 nuclear localization and reduced expression of the myocyte enhancer factor 2 (MEF2) transcriptional ..
  32. Han X, Hao C, Li L, Li J, Fang M, Zheng Y, et al. HDAC4 stimulates MRTF-A expression and drives fibrogenesis in hepatic stellate cells by targeting miR-206. Oncotarget. 2017;8:47586-47594 pubmed publisher
    ..Mechanistically, histone deacetylase 4 (HDAC4) was induced by pro-fibrogenic stimuli and recruited to the miR-206 promoter to repress miR-206 ..
  33. Mielcarek M, Landles C, Weiss A, Bradaia A, Seredenina T, Inuabasi L, et al. HDAC4 reduction: a novel therapeutic strategy to target cytoplasmic huntingtin and ameliorate neurodegeneration. PLoS Biol. 2013;11:e1001717 pubmed publisher
    ..We found that HDAC4 associates with huntingtin in a polyglutamine-length-dependent manner and co-localises with cytoplasmic inclusions...
  34. Tiwari S, Dharmarajan S, Shivanna M, Otteson D, Belecky Adams T. Histone deacetylase expression patterns in developing murine optic nerve. BMC Dev Biol. 2014;14:30 pubmed publisher
    ..These HDACs are candidates for further research to understand how chromatin remodeling through acetylation, deacetylation and methylation contributes to glial development as well as their injury response. ..
  35. Yuan H, Denton K, Liu L, Li X, Benashski S, McCullough L, et al. Nuclear translocation of histone deacetylase 4 induces neuronal death in stroke. Neurobiol Dis. 2016;91:182-93 pubmed publisher
    ..b>HDAC4 is highly expressed in neurons and is usually trapped in cytosol...
  36. Ono W, Sakagami N, Nishimori S, Ono N, Kronenberg H. Parathyroid hormone receptor signalling in osterix-expressing mesenchymal progenitors is essential for tooth root formation. Nat Commun. 2016;7:11277 pubmed publisher
    ..Deletion of histone deacetylase-4 (HDAC4) partially recapitulates the PPR deletion root phenotype...
  37. Wang W, Song B, Anbarchian T, Shirazyan A, Sadik J, Lyons K. Smad2 and Smad3 Regulate Chondrocyte Proliferation and Differentiation in the Growth Plate. PLoS Genet. 2016;12:e1006352 pubmed publisher
    ..Furthermore, nuclear localization of the repressor Hdac4 was decreased in growth plates of Smad2CKO and double mutant mice...
  38. Winbanks C, Beyer C, Hagg A, Qian H, Sepulveda P, Gregorevic P. miR-206 represses hypertrophy of myogenic cells but not muscle fibers via inhibition of HDAC4. PLoS ONE. 2013;8:e73589 pubmed publisher
    ..We have previously demonstrated that histone deacetylase 4 (HDAC4) is a target of miR-206 in the regulation of myogenic differentiation...
  39. Mielcarek M, Seredenina T, Stokes M, Osborne G, Landles C, Inuabasi L, et al. HDAC4 does not act as a protein deacetylase in the postnatal murine brain in vivo. PLoS ONE. 2013;8:e80849 pubmed publisher
    ..b>HDAC4, like its class IIa counterparts, is a potent transcriptional repressor through interactions with tissue specific ..
  40. Medford H, Porter K, Marsh S. Immediate effects of a single exercise bout on protein O-GlcNAcylation and chromatin regulation of cardiac hypertrophy. Am J Physiol Heart Circ Physiol. 2013;305:H114-23 pubmed publisher
  41. Berdeaux R, Goebel N, Banaszynski L, Takemori H, WANDLESS T, Shelton G, et al. SIK1 is a class II HDAC kinase that promotes survival of skeletal myocytes. Nat Med. 2007;13:597-603 pubmed
  42. Nakatani T, Chen T, Partridge N. MMP-13 is one of the critical mediators of the effect of HDAC4 deletion on the skeleton. Bone. 2016;90:142-51 pubmed publisher
    b>Histone deacetylase 4 (Hdac4) regulates chondrocyte hypertrophy. Hdac4(-/-) mice are runted in size and do not survive to weaning...
  43. Witt O, Deubzer H, Milde T, Oehme I. HDAC family: What are the cancer relevant targets?. Cancer Lett. 2009;277:8-21 pubmed publisher
    ..The aim of this review is to discuss individual HDAC family members as drug targets in cancer taking into consideration their function under physiological conditions and their oncogenic potential in malignant disease. ..
  44. Papaioannou G, Mirzamohammadi F, Lisse T, Nishimori S, Wein M, Kobayashi T. MicroRNA-140 Provides Robustness to the Regulation of Hypertrophic Chondrocyte Differentiation by the PTHrP-HDAC4 Pathway. J Bone Miner Res. 2015;30:1044-52 pubmed publisher
    ..role in regulation of hypertrophic differentiation, at least in part, through enhancing activity of histone deacetylase 4 (HDAC4), a negative regulator of MEF2 transcription factors that drive hypertrophy...
  45. Zhao Y, Wang H, Zhang S, Du J, Zhuang S, Zhao T. Irisin Ameliorates Hypoxia/Reoxygenation-Induced Injury through Modulation of Histone Deacetylase 4. PLoS ONE. 2016;11:e0166182 pubmed publisher
    ..This study sought to determine the effects of irisin on hypoxia/reoxygenation injury and its relationship with HDAC4. Wild type and stable HDAC4-overexpression cells were generated from H9c2 cardiomyoblasts...
  46. Weems J, Griesel B, Olson A. Class II histone deacetylases downregulate GLUT4 transcription in response to increased cAMP signaling in cultured adipocytes and fasting mice. Diabetes. 2012;61:1404-14 pubmed publisher
    ..Chromatin immunoprecipitation experiments showed the association of HDAC4/5 with the GLUT4 promoter in vivo and in vitro in response to elevated cAMP...
  47. Crow M, Khovanov N, Kelleher J, Sharma S, Grant A, Bogdanov Y, et al. HDAC4 is required for inflammation-associated thermal hypersensitivity. FASEB J. 2015;29:3370-8 pubmed publisher
    Transcriptional alterations are characteristic of persistent pain states, but the key regulators remain elusive. HDAC4 is a transcriptional corepressor that has been linked to synaptic plasticity and neuronal excitability, mechanisms ..
  48. Micheli L, Leonardi L, Conti F, Buanne P, Canu N, Caruso M, et al. PC4 coactivates MyoD by relieving the histone deacetylase 4-mediated inhibition of myocyte enhancer factor 2C. Mol Cell Biol. 2005;25:2242-59 pubmed
    b>Histone deacetylase 4 (HDAC4) negatively regulates skeletal myogenesis by associating with the myocyte enhancer factor 2 (MEF2) transcription factors...
  49. Kang J, Alliston T, Delston R, Derynck R. Repression of Runx2 function by TGF-beta through recruitment of class II histone deacetylases by Smad3. EMBO J. 2005;24:2543-55 pubmed
    ..Accordingly, HDAC4 or 5 is required for efficient TGF-beta-mediated inhibition of Runx2 function and is involved in osteoblast ..
  50. Zhang T, Kohlhaas M, Backs J, Mishra S, Phillips W, Dybkova N, et al. CaMKIIdelta isoforms differentially affect calcium handling but similarly regulate HDAC/MEF2 transcriptional responses. J Biol Chem. 2007;282:35078-87 pubmed
    ..confirmed that CaMKIIdelta(B) and delta(C) both regulate MEF2-luciferase gene expression, increase histone deacetylase 4 (HDAC4) association with 14-3-3, and induce HDAC4 translocation from nucleus to cytoplasm, indicating that ..
  51. Yang Q, Wei J, Zhong L, Shi M, Zhou P, Zuo S, et al. Cross talk between histone deacetylase 4 and STAT6 in the transcriptional regulation of arginase 1 during mouse dendritic cell differentiation. Mol Cell Biol. 2015;35:63-75 pubmed publisher
    ..showed that the induced expression of Arg1 in differentiating DCs was caused by enhanced recruitment of histone deacetylase 4 (HDAC4) to the Arg1 promoter region, which led to a reduction in the acetylation of both the histone 3 and ..
  52. Abend A, Shkedi O, Fertouk M, Caspi L, Kehat I. Salt-inducible kinase induces cytoplasmic histone deacetylase 4 to promote vascular calcification. EMBO Rep. 2017;18:1166-1185 pubmed publisher
    ..We studied VSMCs, mouse aortic rings, and human aortic valves and showed here that histone deacetylase 4 (HDAC4) is upregulated early in the calcification process...
  53. Matsushima S, Kuroda J, Ago T, Zhai P, Park J, Xie L, et al. Increased oxidative stress in the nucleus caused by Nox4 mediates oxidation of HDAC4 and cardiac hypertrophy. Circ Res. 2013;112:651-63 pubmed publisher
    Oxidation of cysteine residues in class II histone deacetylases (HDACs), including HDAC4, causes nuclear exit, thereby inducing cardiac hypertrophy...
  54. Yamaguchi N, Chakraborty A, Pasek D, Molkentin J, Meissner G. Dysfunctional ryanodine receptor and cardiac hypertrophy: role of signaling molecules. Am J Physiol Heart Circ Physiol. 2011;300:H2187-95 pubmed publisher
    ..5 hearts; rather increased Erk1/2 and p90RSK phosphorylation levels likely leading to reduced GSK-3? activity were found to precede development of cardiac hypertrophy in mice expressing dysfunctional ryanodine receptor ion channel. ..
  55. Wang X, Liu J, Zhen J, Zhang C, Wan Q, Liu G, et al. Histone deacetylase 4 selectively contributes to podocyte injury in diabetic nephropathy. Kidney Int. 2014;86:712-25 pubmed publisher
    ..or transforming growth factor-? (common detrimental factors in diabetic nephropathy) selectively increased HDAC4 expression...
  56. Karamboulas C, Swedani A, Ward C, Al Madhoun A, Wilton S, Boisvenue S, et al. HDAC activity regulates entry of mesoderm cells into the cardiac muscle lineage. J Cell Sci. 2006;119:4305-14 pubmed
    Class II histone deacetylases (HDAC4, HDAC5, HDAC7 and HDAC9) have been shown to interact with myocyte enhancer factors 2 (MEF2s) and play an important role in the repression of cardiac hypertrophy...
  57. Usui T, Morita T, Okada M, Yamawaki H. Histone deacetylase 4 controls neointimal hyperplasia via stimulating proliferation and migration of vascular smooth muscle cells. Hypertension. 2014;63:397-403 pubmed publisher
    Histone deacetylases (HDACs) are transcriptional coregulators. Recently, we demonstrated that HDAC4, one of class IIa family members, promotes reactive oxygen species-dependent vascular smooth muscle inflammation and mediates development ..
  58. Li X, Li L, Li J, Sipple J, Schick J, Mehta P, et al. Concomitant inactivation of foxo3a and fancc or fancd2 reveals a two-tier protection from oxidative stress-induced hydrocephalus. Antioxid Redox Signal. 2014;21:1675-92 pubmed publisher
    ..The deletion of Foxo3a in FA mice increased the accumulation of ROS and subsequently de-regulated mitosis and ultimately apoptosis in the NSPCs, leading to hydrocephalus development. ..
  59. Spies N, Smith C, Rodriguez J, Baker J, Batzoglou S, Sidow A. Constraint and divergence of global gene expression in the mammalian embryo. elife. 2015;4:e05538 pubmed publisher
    ..The widespread effect of maternal and embryonic genotype in conjunction with the purifying selection we uncovered suggests that embryogenesis is an important and understudied reservoir of phenotypic variation. ..
  60. Tian F, An L, Wang G, Zhu J, Li Q, Zhang Y, et al. Elevated microRNA-155 promotes foam cell formation by targeting HBP1 in atherogenesis. Cardiovasc Res. 2014;103:100-10 pubmed publisher
    ..Our findings reveal a new regulatory pathway of YY1/HDACs/miR-155/HBP1 in macrophage-derived foam cell formation during early atherogenesis and suggest that miR-155 is a potential therapeutic target for atherosclerosis. ..
  61. Izzi L, Silvestri C, Von Both I, Labbé E, Zakin L, Wrana J, et al. Foxh1 recruits Gsc to negatively regulate Mixl1 expression during early mouse development. EMBO J. 2007;26:3132-43 pubmed
    ..As Gsc is itself induced in a Foxh1-dependent manner, we propose that Foxh1 initiates positive and negative transcriptional circuits to refine cell fate decisions during gastrulation. ..
  62. Zhang M, Hagenmueller M, Riffel J, Kreusser M, Bernhold E, Fan J, et al. Calcium/calmodulin-dependent protein kinase II couples Wnt signaling with histone deacetylase 4 and mediates dishevelled-induced cardiomyopathy. Hypertension. 2015;65:335-44 pubmed publisher
    ..Further mechanistic analyses unveiled that CaMKIIδγ couples noncanonical Wnt signaling to histone deacetylase 4 and myosin enhancer factor 2...
  63. Huang Y, Tiao M, Huang L, Chuang J, Kuo K, Yang Y, et al. Activation of Mir-29a in Activated Hepatic Stellate Cells Modulates Its Profibrogenic Phenotype through Inhibition of Histone Deacetylases 4. PLoS ONE. 2015;10:e0136453 pubmed publisher
    ..In addition, inhibition of the activity of histone deacetylases 4 (HDAC4) has been shown to strongly reduce HSC activation in the context of liver fibrosis...
  64. Lenoir O, Flosseau K, Ma F, Blondeau B, Mai A, Bassel Duby R, et al. Specific control of pancreatic endocrine ?- and ?-cell mass by class IIa histone deacetylases HDAC4, HDAC5, and HDAC9. Diabetes. 2011;60:2861-71 pubmed publisher
    ..We took a genetic approach and analyzed the pancreatic phenotype of mice lacking HDAC4, -5, and -9...
  65. Ferreira R, Popova E, James J, Briones M, Zhang S, Barnstable C. Histone Deacetylase 1 Is Essential for Rod Photoreceptor Differentiation by Regulating Acetylation at Histone H3 Lysine 9 and Histone H4 Lysine 12 in the Mouse Retina. J Biol Chem. 2017;292:2422-2440 pubmed publisher
    ..HDAC1 may be an essential epigenetic regulator of the transition from progenitor cells to terminally differentiated photoreceptors. ..
  66. Jeong B, Hong C, Chattopadhyay S, Park J, Gong E, Kim H, et al. Androgen receptor corepressor-19 kDa (ARR19), a leucine-rich protein that represses the transcriptional activity of androgen receptor through recruitment of histone deacetylase. Mol Endocrinol. 2004;18:13-25 pubmed
    ..The ARR19 repression of AR transactivation is through the recruitment of histone deacetylase 4 (HDAC4) by ARR19. Overexpression of HDAC4 further inhibits the ARR19-repressed AR transactivation...
  67. Gaur V, Connor T, Sanigorski A, Martin S, Bruce C, Henstridge D, et al. Disruption of the Class IIa HDAC Corepressor Complex Increases Energy Expenditure and Lipid Oxidation. Cell Rep. 2016;16:2802-2810 pubmed publisher
    ..Therefore, compounds that disrupt class IIa HDAC function could be used to enhance metabolic health in chronic diseases driven by physical inactivity. ..
  68. Mu P, Deepak V, Kang L, Jiang Q, Liu R, Meng L, et al. Ratjadone C-mediated nuclear accumulation of HDAC4: implications on Runx2-induced osteoblast differentiation of C3H10T1/2 mesenchymal stem cells. Z Naturforsch C. 2014;69:471-8 pubmed publisher
    ..b>HDAC4, a class-IIa HDAC, has been reported to shuttle between nucleus and cytoplasm in response to various cellular ..
  69. Han X, Niu J, Zhao Y, Kong Q, Tong T, Han L. HDAC4 stabilizes SIRT1 via sumoylation SIRT1 to delay cellular senescence. Clin Exp Pharmacol Physiol. 2016;43:41-6 pubmed publisher
    ..b>Histone deacetylase 4 (HDAC4) belongs to the class IIa group of HDACs; this class of HDACs is composed of proteins that are ..
  70. Sen T, Sen N. Isoflurane-induced inactivation of CREB through histone deacetylase 4 is responsible for cognitive impairment in developing brain. Neurobiol Dis. 2016;96:12-21 pubmed publisher
    ..and the alterations in acetylation of histones modulated by several histone deacetylases such as HDAC4 (histone deacetylase 4) are known to contribute to synaptic plasticity in the brain...
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    ..Specifically, AP5 altered the expression of all three class IIa HDACs that are highly expressed in the brain, HDAC4, HDAC5, and HDAC9, and also induced nuclear accumulation of HDAC4...
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    b>Histone deacetylase 4 (HDAC4) and its paralogs, HDAC5, -7, and -9 (all members of class IIa), possess multiple phosphorylation sites crucial for 14-3-3 binding and subsequent nuclear export...