histone deacetylase 5


Gene Symbol: histone deacetylase 5
Description: histone deacetylase 5
Alias: histone deacetylase 5
Species: rat
Products:     histone deacetylase 5

Top Publications

  1. McKinsey T, Zhang C, Lu J, Olson E. Signal-dependent nuclear export of a histone deacetylase regulates muscle differentiation. Nature. 2000;408:106-11 pubmed
  2. Renthal W, Maze I, Krishnan V, Covington H, Xiao G, Kumar A, et al. Histone deacetylase 5 epigenetically controls behavioral adaptations to chronic emotional stimuli. Neuron. 2007;56:517-29 pubmed
  3. Grozinger C, Schreiber S. Regulation of histone deacetylase 4 and 5 and transcriptional activity by 14-3-3-dependent cellular localization. Proc Natl Acad Sci U S A. 2000;97:7835-40 pubmed
    ..Regulation of the cellular localization of HDAC4 and HDAC5 by 14-3-3 represents a mechanism for controlling the transcriptional activity of these class II HDAC proteins. ..
  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. Backs J, Song K, Bezprozvannaya S, Chang S, Olson E. CaM kinase II selectively signals to histone deacetylase 4 during cardiomyocyte hypertrophy. J Clin Invest. 2006;116:1853-64 pubmed
    ..These findings reveal a central role for HDAC4 in CaMKII signaling pathways and have implications for the control of gene expression by calcium signaling in a variety of cell types. ..
  6. Gomez Pinilla F, Zhuang Y, Feng J, Ying Z, Fan G. Exercise impacts brain-derived neurotrophic factor plasticity by engaging mechanisms of epigenetic regulation. Eur J Neurosci. 2011;33:383-90 pubmed publisher
    ..Exercise also reduces levels of the histone deacetylase 5 mRNA and protein implicated in the regulation of the Bdnf gene [N.M. Tsankova et al. (2006)Nat. Neurosci...
  7. Lin S, Sterling N, Junker I, Helm C, Smith G. Effects of ?TAT1 and HDAC5 on axonal regeneration in adult neurons. PLoS ONE. 2017;12:e0177496 pubmed publisher
    ..Thus, while ?TAT1 may be important for axonal growth in vitro, neither ?TAT1 nor HDAC5 had an effect in vivo on the regeneration of sciatic nerves. ..
  8. Hsing C, Lin C, So E, Sun D, Chen T, Li C, et al. ?2-Adrenoceptor agonist dexmedetomidine protects septic acute kidney injury through increasing BMP-7 and inhibiting HDAC2 and HDAC5. Am J Physiol Renal Physiol. 2012;303:F1443-53 pubmed publisher
    ..However, DEX treatment reduced those changes. DEX reduces sepsis-induced AKI by decreasing TNF-? and MCP-1 and increasing BMP-7, which is associated with decreasing HDAC2 and HDAC5, as well as increasing acetyl histone H3. ..
  9. Klappacher G, Lunyak V, Sykes D, Sawka Verhelle D, Sage J, Brard G, et al. An induced Ets repressor complex regulates growth arrest during terminal macrophage differentiation. Cell. 2002;109:169-80 pubmed

More Information


  1. Chandrasekaran S, Peterson R, Mani S, Addy B, Buchholz A, Xu L, et al. Histone deacetylases facilitate sodium/calcium exchanger up-regulation in adult cardiomyocytes. FASEB J. 2009;23:3851-64 pubmed publisher
    ..We propose a novel model for Ncx1 regulation in which deacetylation of Nkx2.5 is required for the recruitment of p300 and results in up-regulation of exchanger expression. ..
  2. Yoshida T, Gan Q, Owens G. Kruppel-like factor 4, Elk-1, and histone deacetylases cooperatively suppress smooth muscle cell differentiation markers in response to oxidized phospholipids. Am J Physiol Cell Physiol. 2008;295:C1175-82 pubmed publisher
    ..Coimmunoprecipitation assays showed that Klf4 interacted with HDAC5. Results provide evidence that Klf4, Elk-1, and HDACs coordinately mediate POVPC-induced suppression of SMC differentiation marker genes. ..
  3. 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. ..
  4. 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
  5. Lemercier C, Verdel A, Galloo B, Curtet S, Brocard M, Khochbin S. mHDA1/HDAC5 histone deacetylase interacts with and represses MEF2A transcriptional activity. J Biol Chem. 2000;275:15594-9 pubmed
  6. Ginnan R, Sun L, Schwarz J, Singer H. MEF2 is regulated by CaMKII?2 and a HDAC4-HDAC5 heterodimer in vascular smooth muscle cells. Biochem J. 2012;444:105-14 pubmed publisher
    ..Taken together, these results illustrate a mechanism by which CaMKII?(2) mediates MEF2-dependent gene transcription in VSMCs through regulation of HDAC4 and HDAC5. ..
  7. Zhang H, Shao Z, Alibin C, Acosta C, Anderson H. Liganded peroxisome proliferator-activated receptors (PPARs) preserve nuclear histone deacetylase 5 levels in endothelin-treated Sprague-Dawley rat cardiac myocytes. PLoS ONE. 2014;9:e115258 pubmed publisher
    ..We focused on export of histone deacetylase 5 (HDAC5) from the nucleus, a key event during hypertrophy, since crosstalk occurs between PPARs and other ..
  8. Potter G, Beaudoin G, DeRenzo C, Zarach J, Chen S, Thompson C. The hairless gene mutated in congenital hair loss disorders encodes a novel nuclear receptor corepressor. Genes Dev. 2001;15:2687-701 pubmed
    ..The discovery that Hr is a corepressor provides a molecular basis for specific hair loss syndromes in both humans and mice. ..
  9. Sun G, Alzayady K, Stewart R, Ye P, Yang S, Li W, et al. Histone demethylase LSD1 regulates neural stem cell proliferation. Mol Cell Biol. 2010;30:1997-2005 pubmed publisher
    ..These findings revealed a novel role for LSD1 in neural stem cell proliferation and uncovered a mechanism for neural stem cell proliferation through recruitment of LSD1 to modulate TLX activity...
  10. Stypula Cyrus Y, Damania D, Kunte D, Cruz M, Subramanian H, Roy H, et al. HDAC up-regulation in early colon field carcinogenesis is involved in cell tumorigenicity through regulation of chromatin structure. PLoS ONE. 2013;8:e64600 pubmed publisher
    ..Together, these results demonstrate the importance of HDAC activity in early carcinogenic events and the unique role of higher-order chromatin structure in determining cell tumorigenicity. ..
  11. Baertschi S, Baur N, Lueders Lefevre V, Voshol J, Keller H. Class I and IIa histone deacetylases have opposite effects on sclerostin gene regulation. J Biol Chem. 2014;289:24995-5009 pubmed publisher
    ..These findings suggest that PTH-mediated Sost repression involves nuclear accumulation of HDAC inhibiting the MEF2-dependent Sost bone enhancer, and class I HDACs are required for constitutive Sost expression in osteocytes. ..
  12. Ajamian F, Suuronen T, Salminen A, Reeben M. Upregulation of class II histone deacetylases mRNA during neural differentiation of cultured rat hippocampal progenitor cells. Neurosci Lett. 2003;346:57-60 pubmed
    ..mRNAs for HDAC 4, 8 and 10 were not detectable by Northern analysis. We suggest that the changes in HDAC mRNA expression levels might be connected with chromatin rearrangement during neural differentiation. ..
  13. Cao D, Wang Z, Zhang C, Oh J, Xing W, Li S, et al. Modulation of smooth muscle gene expression by association of histone acetyltransferases and deacetylases with myocardin. Mol Cell Biol. 2005;25:364-76 pubmed
    ..These findings point to myocardin as a nexus for positive and negative regulation of smooth muscle gene expression by changes in chromatin acetylation. ..
  14. 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
  15. Harrison B, Huynh K, Lundgaard G, Helmke S, Perryman M, McKinsey T. Protein kinase C-related kinase targets nuclear localization signals in a subset of class IIa histone deacetylases. FEBS Lett. 2010;584:1103-10 pubmed publisher
    ..We provide evidence to suggest that the unique phospho-acceptor cooperates with the 14-3-3 target sites to impair HDAC nuclear import. ..
  16. Mukwevho E, Kohn T, Lang D, Nyatia E, Smith J, Ojuka E. Caffeine induces hyperacetylation of histones at the MEF2 site on the Glut4 promoter and increases MEF2A binding to the site via a CaMK-dependent mechanism. Am J Physiol Endocrinol Metab. 2008;294:E582-8 pubmed publisher
    ..These data indicate that caffeine increases GLUT4 expression by acetylating the MEF2 site to increase MEF2A binding via a mechanism that involves CaMK II. ..
  17. Li N, Yuan Q, Cao X, Zhang Y, Min Z, Xu S, et al. Opposite effects of HDAC5 and p300 on MRTF-A-related neuronal apoptosis during ischemia/reperfusion injury in rats. Cell Death Dis. 2017;8:e2624 pubmed publisher
    ..b>Histone deacetylase 5 (HDAC5) and histone acetyltransferase p300 (P300) are two well-known regulators for transcription factors; ..
  18. Weeks K, Ranieri A, Karaś A, Bernardo B, Ashcroft A, Molenaar C, et al. ?-Adrenergic Stimulation Induces Histone Deacetylase 5 (HDAC5) Nuclear Accumulation in Cardiomyocytes by B55?-PP2A-Mediated Dephosphorylation. J Am Heart Assoc. 2017;6: pubmed publisher
  19. Pang J, Yan C, Natarajan K, Cavet M, Massett M, Yin G, et al. GIT1 mediates HDAC5 activation by angiotensin II in vascular smooth muscle cells. Arterioscler Thromb Vasc Biol. 2008;28:892-8 pubmed publisher
    ..This study identifies a novel function for GIT1 as a mediator of Ang II-induced VSMC gene transcription via a Src-PLCgamma-CamK II-HDAC5 signaling pathway. ..
  20. Sucharov C, Dockstader K, McKinsey T. YY1 protects cardiac myocytes from pathologic hypertrophy by interacting with HDAC5. Mol Biol Cell. 2008;19:4141-53 pubmed publisher
    ..function of YY1 as a repressor in cardiac myocytes is tightly dependent on its ability to interact with histone deacetylase 5 (HDAC5)...
  21. Sakao Y, Kato A, Tsuji T, Yasuda H, Togawa A, Fujigaki Y, et al. Cisplatin induces Sirt1 in association with histone deacetylation and increased Werner syndrome protein in the kidney. Clin Exp Nephrol. 2011;15:363-372 pubmed publisher
    ..The induced Sirt1 may work defensively to mitigate CDDP-induced tubular damage by inactivating core histone transcriptionally, and by repairing DNA damage. ..
  22. Zhao L, Chen C, Hajji N, Oliver E, Cotroneo E, Wharton J, et al. Histone deacetylation inhibition in pulmonary hypertension: therapeutic potential of valproic acid and suberoylanilide hydroxamic acid. Circulation. 2012;126:455-67 pubmed publisher
    ..The effectiveness of HDAC inhibitors, valproic acid, and suberoylanilide hydroxamic acid, in models of pulmonary arterial hypertension supports a therapeutic strategy based on HDAC inhibition in pulmonary arterial hypertension. ..
  23. Chang C, Cheong M, Chang G, Tsai M, Chen H. Involvement of Epac1/Rap1/CaMKI/HDAC5 signaling cascade in the regulation of placental cell fusion. Mol Hum Reprod. 2013;19:745-55 pubmed publisher
    ..Our results reveal a new layer of regulation of GCM1 activity and placental cell fusion through the Epac1/Rap1/CaMKI signaling cascade by restraining HDAC5 from interacting with and mediating GCM1 deacetylation. ..
  24. Lu J, McKinsey T, Zhang C, Olson E. Regulation of skeletal myogenesis by association of the MEF2 transcription factor with class II histone deacetylases. Mol Cell. 2000;6:233-44 pubmed
    ..These findings reveal central roles for HDACs in chromatin remodeling during myogenesis and as intranuclear targets for signaling pathways controlled by IGF and CaM kinase. ..
  25. Nakagawa Y, Kuwahara K, Harada M, Takahashi N, Yasuno S, Adachi Y, et al. Class II HDACs mediate CaMK-dependent signaling to NRSF in ventricular myocytes. J Mol Cell Cardiol. 2006;41:1010-22 pubmed
  26. Xia S, Li X, Johnson T, Seidel C, Wallace D, Li R. Polycystin-dependent fluid flow sensing targets histone deacetylase 5 to prevent the development of renal cysts. Development. 2010;137:1075-84 pubmed publisher
    ..Here, we found that myocyte enhancer factor 2C (MEF2C) and histone deacetylase 5 (HDAC5), two key regulators of cardiac hypertrophy, are targets of polycystin-dependent fluid stress ..
  27. Jo H, Kim Y, Son H. Erythropoietin and carbamylated erythropoietin promote histone deacetylase 5 phosphorylation and nuclear export in rat hippocampal neurons. Biochem Biophys Res Commun. 2016;470:220-225 pubmed publisher
    ..Here, we show a previously unidentified role of histone deacetylase 5 (HDAC5) in the actions of EPO and cEPO...
  28. Xu X, Ha C, Wong C, Wang W, Hausser A, Pfizenmaier K, et al. Angiotensin II stimulates protein kinase D-dependent histone deacetylase 5 phosphorylation and nuclear export leading to vascular smooth muscle cell hypertrophy. Arterioscler Thromb Vasc Biol. 2007;27:2355-62 pubmed
  29. 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
    ..Our results indicate that class IIa HDACs act as corepressors for TGF-beta/Smad3-mediated transcriptional repression of Runx2 function in differentiating osteoblasts and are cell-intrinsic regulators of osteoblast differentiation. ..
  30. Urbich C, Rossig L, Kaluza D, Potente M, Boeckel J, Knau A, et al. HDAC5 is a repressor of angiogenesis and determines the angiogenic gene expression pattern of endothelial cells. Blood. 2009;113:5669-79 pubmed publisher
    ..The derepression of angiogenic genes by HDAC5 inactivation may provide a useful therapeutic target for induction of angiogenesis. ..
  31. Bers D. Ca²?-calmodulin-dependent protein kinase II regulation of cardiac excitation-transcription coupling. Heart Rhythm. 2011;8:1101-4 pubmed publisher
  32. 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
    ..Thus, HDAC4 contributes to podocyte injury and is one of critical components of a signal transduction pathway that links renal injury to autophagy in diabetic nephropathy. ..
  33. Linseman D, Bartley C, Le S, Laessig T, Bouchard R, Meintzer M, et al. Inactivation of the myocyte enhancer factor-2 repressor histone deacetylase-5 by endogenous Ca(2+) //calmodulin-dependent kinase II promotes depolarization-mediated cerebellar granule neuron survival. J Biol Chem. 2003;278:41472-81 pubmed
    ..These results indicate that depolarization-mediated calcium influx acts through CaMKII to inhibit HDAC5, thereby sustaining high MEF2 activity in CGNs maintained under depolarizing conditions. ..
  34. Kao H, Downes M, Ordentlich P, Evans R. Isolation of a novel histone deacetylase reveals that class I and class II deacetylases promote SMRT-mediated repression. Genes Dev. 2000;14:55-66 pubmed
    ..Taken together, our results provide the first evidence that SMRT-mediated repression is promoted by class I and class II histone deacetylases and that SMRT can recruit class II histone deacetylases in a mSin3A-independent fashion. ..
  35. Zhang C, McKinsey T, Olson E. Association of class II histone deacetylases with heterochromatin protein 1: potential role for histone methylation in control of muscle differentiation. Mol Cell Biol. 2002;22:7302-12 pubmed
  36. Taniguchi M, Carreira M, Cooper Y, Bobadilla A, Heinsbroek J, Koike N, et al. HDAC5 and Its Target Gene, Npas4, Function in the Nucleus Accumbens to Regulate Cocaine-Conditioned Behaviors. Neuron. 2017;96:130-144.e6 pubmed publisher
    ..We found that dephosphorylated, nuclear histone deacetylase 5 (HDAC5) in the nucleus accumbens (NAc) reduced cocaine reward-context associations and relapse-like ..
  37. Seo H, Kim E, Na H, Lee M. Transcriptional activation of hypoxia-inducible factor-1alpha by HDAC4 and HDAC5 involves differential recruitment of p300 and FIH-1. FEBS Lett. 2009;583:55-60 pubmed publisher
    ..These results indicate that HDAC4 and HDAC5 increase the transactivation function of HIF-1alpha by promoting dissociation of HIF-1alpha from FIH-1 and association with p300. ..
  38. Long X, Creemers E, Wang D, Olson E, Miano J. Myocardin is a bifunctional switch for smooth versus skeletal muscle differentiation. Proc Natl Acad Sci U S A. 2007;104:16570-5 pubmed
    ..This repressor function of Myocd is complex, involving histone deacetylase 5 silencing of the Myog promoter and Myocd's physical contact with MyoD, which undermines MyoD DNA binding ..
  39. Chang C, Lee L, Yu D, Dao K, Bossuyt J, Bers D. Acute ?-adrenergic activation triggers nuclear import of histone deacetylase 5 and delays G(q)-induced transcriptional activation. J Biol Chem. 2013;288:192-204 pubmed publisher
    ..Dynamic regulation of histone deacetylase 5 (HDAC5), a transcriptional repressor, is crucial during stress signaling due to its role in epigenetic ..
  40. Liu D, Qiu H, Fei H, Hu X, Xia H, Wang L, et al. Histone acetylation and expression of mono-aminergic transmitters synthetases involved in CUS-induced depressive rats. Exp Biol Med (Maywood). 2014;239:330-6 pubmed publisher
    ..Administration of sodium valproate (VPA), a histone deacetylase 5 (HDAC5) inhibitor, not only significantly relieved the anxiety- and depression-like behaviors of CUS-..
  41. Dietrich J, Takemori H, Grosch Dirrig S, Bertorello A, Zwiller J. Cocaine induces the expression of MEF2C transcription factor in rat striatum through activation of SIK1 and phosphorylation of the histone deacetylase HDAC5. Synapse. 2012;66:61-70 pubmed publisher
    ..Since MEF2C plays a key role in memory/learning processes, activation of this pathway by cocaine is probably involved in plasticity mechanisms whereby the drug establishes its long-term effects such as drug dependence. ..
  42. Wei J, Lu Q, Li W, He W. Intracellular translocation of histone deacetylase 5 regulates neuronal cell apoptosis. Brain Res. 2015;1604:15-24 pubmed publisher
    b>Histone deacetylase 5 (HDAC5) undergoes signal-dependent shuttling between the nucleus and cytoplasm, which is regulated in part by calcium/calmodulin-dependent kinase (CaMK)-mediated phosphorylation...
  43. DasBanerjee T, Middleton F, Berger D, Lombardo J, Sagvolden T, Faraone S. A comparison of molecular alterations in environmental and genetic rat models of ADHD: a pilot study. Am J Med Genet B Neuropsychiatr Genet. 2008;147B:1554-63 pubmed publisher
    ..The data provide strong evidence that genes and environment can affect different set of genes in two different models of ADHD and yet result in the similar disease-like symptoms. ..
  44. He M, Zhang B, Wei X, Wang Z, Fan B, Du P, et al. HDAC4/5-HMGB1 signalling mediated by NADPH oxidase activity contributes to cerebral ischaemia/reperfusion injury. J Cell Mol Med. 2013;17:531-42 pubmed publisher
  45. Kang H, Lee M, Kang H, Kim S, Ahn J, Na H, et al. Differential regulation of estrogen receptor ? expression in breast cancer cells by metastasis-associated protein 1. Cancer Res. 2014;74:1484-94 pubmed publisher
  46. McKinsey T, Kuwahara K, Bezprozvannaya S, Olson E. Class II histone deacetylases confer signal responsiveness to the ankyrin-repeat proteins ANKRA2 and RFXANK. Mol Biol Cell. 2006;17:438-47 pubmed
    ..These results define a novel transcriptional pathway under the control of class II HDACs and suggest a role for these transcriptional repressors as signal-responsive regulators of antigen presentation. ..
  47. Spiegelberg B, Hamm H. G betagamma binds histone deacetylase 5 (HDAC5) and inhibits its transcriptional co-repression activity. J Biol Chem. 2005;280:41769-76 pubmed
    ..effectors of the G betagamma subunit of heterotrimeric G proteins, we found that G betagamma binds to histone deacetylase 5 (HDAC5), an enzyme involved in a pathway not previously recognized to be directly impacted by G proteins...
  48. Chen H, Qi L. SUMO modification regulates the transcriptional activity of XBP1. Biochem J. 2010;429:95-102 pubmed publisher
    ..Thus our results reveal an unexpected role for SUMO (small ubiquitin-related modifier) in the regulation of UPR activation and ER homeostasis. ..
  49. Dai Y, Xu J, Molkentin J. The DnaJ-related factor Mrj interacts with nuclear factor of activated T cells c3 and mediates transcriptional repression through class II histone deacetylase recruitment. Mol Cell Biol. 2005;25:9936-48 pubmed
    ..Collectively, our results define a novel response pathway whereby NFATc3 is negatively regulated by class II histone deacetylases through the DnaJ (heat shock protein-40) superfamily member Mrj. ..
  50. Fu X, Zhao J, Liang J, Zhu M, Foretz M, Viollet B, et al. AMP-activated protein kinase mediates myogenin expression and myogenesis via histone deacetylase 5. Am J Physiol Cell Physiol. 2013;305:C887-95 pubmed publisher
    ..We postulated that AMPK regulates myogenin expression through phosphorlytion of histone deacetylase 5 (HDAC5)...