HDAC4 Available structures PDB Ortholog search:PDBe RCSB List of PDB id codes 2H8N ,2O94 ,2VQJ ,2VQM ,2VQO ,2VQQ ,2VQV ,2VQW ,3UXG ,3UZD ,3V31 ,4CBT ,4CBY ,5A2S
Identifiers Aliases HDAC4 External IDs OMIM :605314 ;MGI :3036234 ;HomoloGene :55946 ;GeneCards :HDAC4 ;OMA :HDAC4 - orthologs Wikidata
Histone deacetylase 4 , also known asHDAC4 , is aprotein that in humans is encoded by theHDAC4 gene .[ 5] [ 6]
Histones play a critical role intranscriptional regulation ,cell cycle progression, and developmental events. Histoneacetylation /deacetylation alterschromosome structure and affects transcription factor access to DNA. The protein encoded by this gene belongs to class II of thehistone deacetylase /acuc/apha family. It possesses histone deacetylase activity and represses transcription when tethered to a promoter. This protein does not bind DNA directly but throughtranscription factors MEF2C andMEF2D . It seems to interact in a multiprotein complex with RbAp48 and HDAC3.[ 7] [ 8]
Clinical significance [ edit ] Studies have shown that HDAC4 regulates bone and muscle development.Harvard University researchers also concluded that it promotes healthy vision: Reduced levels of the protein led to the death of the rodphotoreceptors and bipolar cells in theretinas of mice.[ 9] [ 10]
HDAC4 has been shown tointeract with:
BCL6 ,[ 11] BTG2 ,[ 12] [ 13] CBX5 ,[ 14] GATA1 ,[ 15] HDAC3 ,[ 5] [ 16] [ 17] [ 18] MAPK1 ,[ 19] MAPK3 ,[ 19] MEF2C ,[ 20] [ 21] Myocyte-specific enhancer factor 2A ,[ 22] [ 23] Nuclear receptor co-repressor 1 ,[ 16] [ 24] Nuclear receptor co-repressor 2 ,[ 16] [ 24] Testicular receptor 2 ,[ 25] [ 26] YWHAB ,[ 17] YWHAE ,[ 17] [ 27] Zinc finger and BTB domain-containing protein 16 .[ 11] [ 28]
^a b c GRCh38: Ensembl release 89: ENSG00000068024 –Ensembl , May 2017^a b c GRCm38: Ensembl release 89: ENSMUSG00000026313 –Ensembl , May 2017^ "Human PubMed Reference:" .National Center for Biotechnology Information, U.S. National Library of Medicine .^ "Mouse PubMed Reference:" .National Center for Biotechnology Information, U.S. National Library of Medicine .^a b Grozinger CM, Hassig CA, Schreiber SL (April 1999)."Three proteins define a class of human histone deacetylases related to yeast Hda1p" .Proceedings of the National Academy of Sciences of the United States of America .96 (9):4868– 73.Bibcode :1999PNAS...96.4868G .doi :10.1073/pnas.96.9.4868 PMC 21783 PMID 10220385 . ^ Fischle W, Emiliani S, Hendzel MJ, Nagase T, Nomura N, Voelter W, Verdin E (April 1999)."A new family of human histone deacetylases related to Saccharomyces cerevisiae HDA1p" .The Journal of Biological Chemistry .274 (17):11713– 20.doi :10.1074/jbc.274.17.11713 PMID 10206986 . ^ "Entrez Gene: HDAC4 histone deacetylase 4" .^ Glenisson W, Castronovo V, Waltregny D (October 2007)."Histone deacetylase 4 is required for TGFbeta1-induced myofibroblastic differentiation" .Biochimica et Biophysica Acta (BBA) - Molecular Cell Research .1773 (10):1572– 82.doi :10.1016/j.bbamcr.2007.05.016 PMID 17610967 . ^ Protein for Sight ,Scientific American ,300 , 3 (March 2009), p. 23^ Chen B, Cepko CL (January 2009)."HDAC4 regulates neuronal survival in normal and diseased retinas" .Science .323 (5911):256– 9.doi :10.1126/science.1166226 .PMC 3339762 PMID 19131628 . ^a b Lemercier C, Brocard MP, Puvion-Dutilleul F, Kao HY, Albagli O, Khochbin S (June 2002)."Class II histone deacetylases are directly recruited by BCL6 transcriptional repressor" .The Journal of Biological Chemistry .277 (24):22045– 52.doi :10.1074/jbc.M201736200 PMID 11929873 . ^ Farioli-Vecchioli S, Tanori M, Micheli L, Mancuso M, Leonardi L, Saran A, Ciotti MT, Ferretti E, Gulino A, Pazzaglia S, Tirone F (July 2007)."Inhibition of medulloblastoma tumorigenesis by the antiproliferative and pro-differentiative gene PC3" .FASEB Journal .21 (9):2215– 25.doi :10.1096/fj.06-7548com PMID 17371797 .S2CID 4974360 . ^ Micheli L, D'Andrea G, Leonardi L, Tirone F (July 2017)."HDAC1, HDAC4, and HDAC9 Bind to PC3/Tis21/Btg2 and Are Required for Its Inhibition of Cell Cycle Progression and Cyclin D1 Expression" (PDF) .Journal of Cellular Physiology .232 (7):1696– 1707.doi :10.1002/jcp.25467 .PMID 27333946 .S2CID 4070837 . ^ Zhang CL, McKinsey TA, Olson EN (October 2002)."Association of class II histone deacetylases with heterochromatin protein 1: potential role for histone methylation in control of muscle differentiation" .Molecular and Cellular Biology .22 (20):7302– 12.doi :10.1128/mcb.22.20.7302-7312.2002 .PMC 139799 PMID 12242305 . ^ Watamoto K, Towatari M, Ozawa Y, Miyata Y, Okamoto M, Abe A, Naoe T, Saito H (December 2003)."Altered interaction of HDAC5 with GATA-1 during MEL cell differentiation" .Oncogene .22 (57):9176– 84.doi :10.1038/sj.onc.1206902 PMID 14668799 . ^a b c Fischle W, Dequiedt F, Hendzel MJ, Guenther MG, Lazar MA, Voelter W, Verdin E (January 2002). "Enzymatic activity associated with class II HDACs is dependent on a multiprotein complex containing HDAC3 and SMRT/N-CoR".Molecular Cell .9 (1):45– 57.doi :10.1016/s1097-2765(01)00429-4 .hdl :11858/00-001M-0000-002C-9FF9-9 PMID 11804585 . ^a b c Grozinger CM, Schreiber SL (July 2000)."Regulation of histone deacetylase 4 and 5 and transcriptional activity by 14-3-3-dependent cellular localization" .Proceedings of the National Academy of Sciences of the United States of America .97 (14):7835– 40.Bibcode :2000PNAS...97.7835G .doi :10.1073/pnas.140199597 PMC 16631 PMID 10869435 . ^ Fischle W, Dequiedt F, Fillion M, Hendzel MJ, Voelter W, Verdin E (September 2001)."Human HDAC7 histone deacetylase activity is associated with HDAC3 in vivo" .The Journal of Biological Chemistry .276 (38):35826– 35.doi :10.1074/jbc.M104935200 PMID 11466315 . ^a b Zhou X, Richon VM, Wang AH, Yang XJ, Rifkind RA, Marks PA (December 2000)."Histone deacetylase 4 associates with extracellular signal-regulated kinases 1 and 2, and its cellular localization is regulated by oncogenic Ras" .Proceedings of the National Academy of Sciences of the United States of America .97 (26):14329– 33.Bibcode :2000PNAS...9714329Z .doi :10.1073/pnas.250494697 PMC 18918 PMID 11114188 . ^ Wang AH, Bertos NR, Vezmar M, Pelletier N, Crosato M, Heng HH, Th'ng J, Han J, Yang XJ (November 1999)."HDAC4, a human histone deacetylase related to yeast HDA1, is a transcriptional corepressor" .Molecular and Cellular Biology .19 (11):7816– 27.doi :10.1128/mcb.19.11.7816 .PMC 84849 PMID 10523670 . ^ Wang AH, Yang XJ (September 2001)."Histone deacetylase 4 possesses intrinsic nuclear import and export signals" .Molecular and Cellular Biology .21 (17):5992– 6005.doi :10.1128/mcb.21.17.5992-6005.2001 .PMC 87317 PMID 11486037 . ^ Miska EA, Karlsson C, Langley E, Nielsen SJ, Pines J, Kouzarides T (September 1999)."HDAC4 deacetylase associates with and represses the MEF2 transcription factor" .The EMBO Journal .18 (18):5099– 107.doi :10.1093/emboj/18.18.5099 .PMC 1171580 PMID 10487761 . ^ Lemercier C, Verdel A, Galloo B, Curtet S, Brocard MP, Khochbin S (May 2000)."mHDA1/HDAC5 histone deacetylase interacts with and represses MEF2A transcriptional activity" (PDF) .The Journal of Biological Chemistry .275 (20):15594– 9.doi :10.1074/jbc.M908437199 PMID 10748098 .S2CID 39220205 . ^a b Huang EY, Zhang J, Miska EA, Guenther MG, Kouzarides T, Lazar MA (January 2000)."Nuclear receptor corepressors partner with class II histone deacetylases in a Sin3-independent repression pathway" .Genes & Development .14 (1):45– 54.doi :10.1101/gad.14.1.45 .PMC 316335 PMID 10640275 . ^ Franco PJ, Li G, Wei LN (August 2003). "Interaction of nuclear receptor zinc finger DNA binding domains with histone deacetylase".Molecular and Cellular Endocrinology .206 (1– 2):1– 12.doi :10.1016/s0303-7207(03)00254-5 .PMID 12943985 .S2CID 19487189 . ^ Franco PJ, Farooqui M, Seto E, Wei LN (August 2001)."The orphan nuclear receptor TR2 interacts directly with both class I and class II histone deacetylases" .Molecular Endocrinology .15 (8):1318– 28.doi :10.1210/mend.15.8.0682 PMID 11463856 . ^ Miska EA, Langley E, Wolf D, Karlsson C, Pines J, Kouzarides T (August 2001)."Differential localization of HDAC4 orchestrates muscle differentiation" .Nucleic Acids Research .29 (16):3439– 47.doi :10.1093/nar/29.16.3439 .PMC 55849 PMID 11504882 . ^ Chauchereau A, Mathieu M, de Saintignon J, Ferreira R, Pritchard LL, Mishal Z, Dejean A, Harel-Bellan A (November 2004)."HDAC4 mediates transcriptional repression by the acute promyelocytic leukaemia-associated protein PLZF" .Oncogene .23 (54):8777– 84.doi :10.1038/sj.onc.1208128 PMID 15467736 . Pazin MJ, Kadonaga JT (May 1997)."What's up and down with histone deacetylation and transcription?" .Cell .89 (3):325– 8.doi :10.1016/S0092-8674(00)80211-1 PMID 9150131 .S2CID 11488594 . Verdin E, Dequiedt F, Kasler HG (May 2003). "Class II histone deacetylases: versatile regulators".Trends in Genetics .19 (5):286– 93.doi :10.1016/S0168-9525(03)00073-8 .hdl :2268/80861 PMID 12711221 . Andersson B, Wentland MA, Ricafrente JY, Liu W, Gibbs RA (April 1996). "A "double adaptor" method for improved shotgun library construction".Analytical Biochemistry .236 (1):107– 13.doi :10.1006/abio.1996.0138 .PMID 8619474 . Yu W, Andersson B, Worley KC, Muzny DM, Ding Y, Liu W, Ricafrente JY, Wentland MA, Lennon G, Gibbs RA (April 1997)."Large-scale concatenation cDNA sequencing" .Genome Research .7 (4):353– 8.doi :10.1101/gr.7.4.353 .PMC 139146 PMID 9110174 . Wolffe AP (May 1997)."Transcriptional control. Sinful repression" .Nature .387 (6628):16– 7.doi :10.1038/387016a0 PMID 9139815 .S2CID 29803420 . Ohara O, Nagase T, Ishikawa K, Nakajima D, Ohira M, Seki N, Nomura N (February 1997)."Construction and characterization of human brain cDNA libraries suitable for analysis of cDNA clones encoding relatively large proteins" .DNA Research .4 (1):53– 9.doi :10.1093/dnares/4.1.53 PMID 9179496 . Fischle W, Emiliani S, Hendzel MJ, Nagase T, Nomura N, Voelter W, Verdin E (April 1999)."A new family of human histone deacetylases related to Saccharomyces cerevisiae HDA1p" .The Journal of Biological Chemistry .274 (17):11713– 20.doi :10.1074/jbc.274.17.11713 PMID 10206986 . Grozinger CM, Hassig CA, Schreiber SL (April 1999)."Three proteins define a class of human histone deacetylases related to yeast Hda1p" .Proceedings of the National Academy of Sciences of the United States of America .96 (9):4868– 73.Bibcode :1999PNAS...96.4868G .doi :10.1073/pnas.96.9.4868 PMC 21783 PMID 10220385 . Miska EA, Karlsson C, Langley E, Nielsen SJ, Pines J, Kouzarides T (September 1999)."HDAC4 deacetylase associates with and represses the MEF2 transcription factor" .The EMBO Journal .18 (18):5099– 107.doi :10.1093/emboj/18.18.5099 .PMC 1171580 PMID 10487761 . Wang AH, Bertos NR, Vezmar M, Pelletier N, Crosato M, Heng HH, Th'ng J, Han J, Yang XJ (November 1999)."HDAC4, a human histone deacetylase related to yeast HDA1, is a transcriptional corepressor" .Molecular and Cellular Biology .19 (11):7816– 27.doi :10.1128/mcb.19.11.7816 .PMC 84849 PMID 10523670 . Youn HD, Grozinger CM, Liu JO (July 2000)."Calcium regulates transcriptional repression of myocyte enhancer factor 2 by histone deacetylase 4" .The Journal of Biological Chemistry .275 (29):22563– 7.doi :10.1074/jbc.C000304200 PMID 10825153 . Grozinger CM, Schreiber SL (July 2000)."Regulation of histone deacetylase 4 and 5 and transcriptional activity by 14-3-3-dependent cellular localization" .Proceedings of the National Academy of Sciences of the United States of America .97 (14):7835– 40.Bibcode :2000PNAS...97.7835G .doi :10.1073/pnas.140199597 PMC 16631 PMID 10869435 . Huynh KD, Fischle W, Verdin E, Bardwell VJ (July 2000)."BCoR, a novel corepressor involved in BCL-6 repression" .Genes & Development .14 (14):1810– 23.doi :10.1101/gad.14.14.1810 .PMC 316791 PMID 10898795 . Li J, Wang J, Wang J, Nawaz Z, Liu JM, Qin J, Wong J (August 2000)."Both corepressor proteins SMRT and N-CoR exist in large protein complexes containing HDAC3" .The EMBO Journal .19 (16):4342– 50.doi :10.1093/emboj/19.16.4342 .PMC 302030 PMID 10944117 . Wang AH, Kruhlak MJ, Wu J, Bertos NR, Vezmar M, Posner BI, Bazett-Jones DP, Yang XJ (September 2000)."Regulation of histone deacetylase 4 by binding of 14-3-3 proteins" .Molecular and Cellular Biology .20 (18):6904– 12.doi :10.1128/MCB.20.18.6904-6912.2000 .PMC 88766 PMID 10958686 . Zhang CL, McKinsey TA, Lu JR, Olson EN (January 2001)."Association of COOH-terminal-binding protein (CtBP) and MEF2-interacting transcription repressor (MITR) contributes to transcriptional repression of the MEF2 transcription factor" .The Journal of Biological Chemistry .276 (1):35– 9.doi :10.1074/jbc.M007364200 PMID 11022042 . McKinsey TA, Zhang CL, Lu J, Olson EN (November 2000)."Signal-dependent nuclear export of a histone deacetylase regulates muscle differentiation" .Nature .408 (6808):106– 11.Bibcode :2000Natur.408..106M .doi :10.1038/35040593 .PMC 4459600 PMID 11081517 . Zhou X, Richon VM, Wang AH, Yang XJ, Rifkind RA, Marks PA (December 2000)."Histone deacetylase 4 associates with extracellular signal-regulated kinases 1 and 2, and its cellular localization is regulated by oncogenic Ras" .Proceedings of the National Academy of Sciences of the United States of America .97 (26):14329– 33.Bibcode :2000PNAS...9714329Z .doi :10.1073/pnas.250494697 PMC 18918 PMID 11114188 . McKinsey TA, Zhang CL, Olson EN (December 2000)."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" .Proceedings of the National Academy of Sciences of the United States of America .97 (26):14400– 5.Bibcode :2000PNAS...9714400M .doi :10.1073/pnas.260501497 PMC 18930 PMID 11114197 . This article incorporates text from theUnited States National Library of Medicine , which is in thepublic domain .
Activity Regulation Classification Kinetics Types
