From Wikipedia, the free encyclopedia
Available structures
PDBOrtholog search: PDBe RCSB
AliasesHDAC3, HD3, RPD3, RPD3-2, histone deacetylase 3
External IDsOMIM: 605166 MGI: 1343091 HomoloGene: 48250 GeneCards: HDAC3
RefSeq (mRNA)



RefSeq (protein)



Location (UCSC)Chr 5: 141.62 – 141.64 MbChr 18: 38.07 – 38.09 Mb
PubMed search[3][4]
View/Edit HumanView/Edit Mouse

Histone deacetylase 3 is an enzyme encoded by the HDAC3 gene in both humans and mice.[5][6][7][8]


Histones are highly alkaline proteins that package and order DNA into structural units called nucleosomes, which comprise the major protein component of chromatin. The posttranslational and enzymatically mediated lysine acetylation and deacetylation of histone tails change the local chromatin structure by altering the electrostatic attraction between the negatively charged DNA backbone and histones. HDAC3 is a Class I member of the histone deacetylase superfamily (comprising four classes based on function and DNA sequence homology) that is recruited to enhancers to modulate both the epigenome and nearby gene expression. HDAC3 is found exclusively in the cell nucleus, where it is the sole endogenous histone deacetylase biochemically purified in the nuclear-receptor corepressor complex containing NCOR and SMRT (NCOR2). Thus, HDAC3, unlike other HDACs, has a unique role in modulating the transcriptional activities of nuclear receptors.

Alternative functions[edit]

Histone deacetylases can be regulated by endogenous factors, dietary components, synthetic inhibitors and bacteria-derived signals. Studies in mice with a specific deletion of HDAC3 in intestinal epithelial cells (IECs) show a deregulated IEC's gene expression. In these deletion-mutant mice, loss of Paneth cells, impaired IEC function and alterations in intestinal composition of commensal bacteria were observed. These negative effects were not observed in germ-free mice, indicating that the effects of the deletion are only seen in the presence of intestinal microbial colonization. But the negative effects of HDAC3 deletion are not due to the presence of an altered microbiota because normal germ-free mice colonized with the altered microbiota did not show the negative effects seen in deletion mutants.

Although the precise mechanism and the specific signals are not known it is clear that HDAC3 interacts with derived signals of commensal bacteria of the gut microbiota. These interactions are responsible of calibrating epithelial cells responses necessary to establish a normal relationship between the host and the commensal as well as to maintain intestinal homeostasis.[9][10][11][12]

Model organisms[edit]

Model organisms have been used in the study of HDAC3 function. A conditional knockout mouse line, called Hdac3tm1a(EUCOMM)Wtsi[17][18] was generated as part of the International Knockout Mouse Consortium program, a high-throughput mutagenesis project to generate and distribute animal models of disease to interested scientists.[19][20][21]

Male and female animals underwent a standardized phenotypic screen to determine the effects of deletion.[15][22]

Twenty six tests were carried out on mutant mice and two significant abnormalities were observed.[15] No homozygous mutant embryos were identified during gestation, and in a separate study none survived until weaning. The remaining tests were carried out on heterozygous mutant adult mice; no significant abnormalities were observed in these animals.[15]


HDAC3 has been shown to interact with:

See also[edit]


  1. ^ a b c GRCh38: Ensembl release 89: ENSG00000171720 - Ensembl, May 2017
  2. ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000024454 - Ensembl, May 2017
  3. ^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  4. ^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  5. ^ Emiliani S, Fischle W, Van Lint C, Al-Abed Y, Verdin E (April 1998). "Characterization of a human RPD3 ortholog, HDAC3". Proc Natl Acad Sci U S A. 95 (6): 2795–800. Bibcode:1998PNAS...95.2795E. doi:10.1073/pnas.95.6.2795. PMC 19648. PMID 9501169.
  6. ^ Dangond F, Hafler DA, Tong JK, Randall J, Kojima R, Utku N, Gullans SR (March 1998). "Differential display cloning of a novel human histone deacetylase (HDAC3) cDNA from PHA-activated immune cells". Biochem Biophys Res Commun. 242 (3): 648–52. doi:10.1006/bbrc.1997.8033. PMID 9464271.
  7. ^ Montgomery, Rusty L.; Potthoff, Matthew J.; Haberland, Michael; Qi, Xiaoxia; Matsuzaki, Satoshi; Humphries, Kenneth M.; Richardson, James A.; Bassel-Duby, Rhonda; Olson, Eric N. (2008-11-03). "Maintenance of cardiac energy metabolism by histone deacetylase 3 in mice". Journal of Clinical Investigation. 118 (11): 3588–3597. doi:10.1172/jci35847. ISSN 0021-9738. PMC 2556240. PMID 18830415.
  8. ^ Bhaskara, Srividya; Chyla, Brenda J.; Amann, Joseph M.; Knutson, Sarah K.; Cortez, David; Sun, Zu-Wen; Hiebert, Scott W. (2008). "Deletion of Histone Deacetylase 3 Reveals Critical Roles in S Phase Progression and DNA Damage Control". Molecular Cell. 30 (1): 61–72. doi:10.1016/j.molcel.2008.02.030. PMC 2373760. PMID 18406327.
  9. ^ Donohoe DR, Bultman SJ (2012). "Metaboloepigenetics: interrelationships between energy metabolism and epigenetic control of gene expression". J. Cell. Physiol. 227 (9): 3169–77. doi:10.1002/jcp.24054. PMC 3338882. PMID 22261928.
  10. ^ Haberland M, Montgomery RL, Olson EN (2009). "The many roles of histone deacetylases in development and physiology: implications for disease and therapy". Nat. Rev. Genet. 10 (1): 32–42. doi:10.1038/nrg2485. PMC 3215088. PMID 19065135.
  11. ^ Kim GW, Gocevski G, Wu CJ, Yang XJ (2010). "Dietary, metabolic, and potentially environmental modulation of the lysine acetylation machinery". Int J Cell Biol. 2010: 1–14. doi:10.1155/2010/632739. PMC 2952894. PMID 20976254.
  12. ^ Dashwood RH, Ho E (2007). "Dietary histone deacetylase inhibitors: from cells to mice to man". Semin. Cancer Biol. 17 (5): 363–9. doi:10.1016/j.semcancer.2007.04.001. PMC 2737738. PMID 17555985.
  13. ^ "Salmonella infection data for Hdac3". Wellcome Trust Sanger Institute.
  14. ^ "Citrobacter infection data for Hdac3". Wellcome Trust Sanger Institute.
  15. ^ a b c d Gerdin AK (2010). "The Sanger Mouse Genetics Programme: High throughput characterisation of knockout mice". Acta Ophthalmologica. 88 (S248). doi:10.1111/j.1755-3768.2010.4142.x. S2CID 85911512.
  16. ^ Mouse Resources Portal, Wellcome Trust Sanger Institute.
  17. ^ "International Knockout Mouse Consortium". Archived from the original on 2012-03-20. Retrieved 2012-01-06.
  18. ^ "Mouse Genome Informatics".
  19. ^ Skarnes WC, Rosen B, West AP, Koutsourakis M, Bushell W, Iyer V, Mujica AO, Thomas M, Harrow J, Cox T, Jackson D, Severin J, Biggs P, Fu J, Nefedov M, de Jong PJ, Stewart AF, Bradley A (2011). "A conditional knockout resource for the genome-wide study of mouse gene function". Nature. 474 (7351): 337–342. doi:10.1038/nature10163. PMC 3572410. PMID 21677750.
  20. ^ Dolgin E (June 2011). "Mouse library set to be knockout". Nature. 474 (7351): 262–3. doi:10.1038/474262a. PMID 21677718.
  21. ^ Collins FS, Rossant J, Wurst W (January 2007). "A mouse for all reasons". Cell. 128 (1): 9–13. doi:10.1016/j.cell.2006.12.018. PMID 17218247. S2CID 18872015.
  22. ^ van der Weyden L, White JK, Adams DJ, Logan DW (2011). "The mouse genetics toolkit: revealing function and mechanism". Genome Biol. 12 (6): 224. doi:10.1186/gb-2011-12-6-224. PMC 3218837. PMID 21722353.
  23. ^ Hoogeveen AT, Rossetti S, Stoyanova V, Schonkeren J, Fenaroli A, Schiaffonati L, van Unen L, Sacchi N (September 2002). "The transcriptional corepressor MTG16a contains a novel nucleolar targeting sequence deranged in t (16; 21)-positive myeloid malignancies". Oncogene. 21 (43): 6703–12. doi:10.1038/sj.onc.1205882. PMID 12242670.
  24. ^ Amann JM, Nip J, Strom DK, Lutterbach B, Harada H, Lenny N, Downing JR, Meyers S, Hiebert SW (October 2001). "ETO, a target of t(8;21) in acute leukemia, makes distinct contacts with multiple histone deacetylases and binds mSin3A through its oligomerization domain". Mol. Cell. Biol. 21 (19): 6470–83. doi:10.1128/MCB.21.19.6470-6483.2001. PMC 99794. PMID 11533236.
  25. ^ Petre-Draviam CE, Williams EB, Burd CJ, Gladden A, Moghadam H, Meller J, Diehl JA, Knudsen KE (January 2005). "A central domain of cyclin D1 mediates nuclear receptor corepressor activity". Oncogene. 24 (3): 431–44. doi:10.1038/sj.onc.1208200. PMID 15558026.
  26. ^ Lin HM, Zhao L, Cheng SY (August 2002). "Cyclin D1 Is a Ligand-independent Co-repressor for Thyroid Hormone Receptors". J. Biol. Chem. 277 (32): 28733–41. doi:10.1074/jbc.M203380200. PMID 12048199.
  27. ^ 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.
  28. ^ Ozawa Y, Towatari M, Tsuzuki S, Hayakawa F, Maeda T, Miyata Y, Tanimoto M, Saito H (October 2001). "Histone deacetylase 3 associates with and represses the transcription factor GATA-2". Blood. 98 (7): 2116–23. doi:10.1182/blood.V98.7.2116. PMID 11567998.
  29. ^ a b c d Zhang J, Kalkum M, Chait BT, Roeder RG (March 2002). "The N-CoR-HDAC3 nuclear receptor corepressor complex inhibits the JNK pathway through the integral subunit GPS2". Mol. Cell. 9 (3): 611–23. doi:10.1016/S1097-2765(02)00468-9. PMID 11931768.
  30. ^ Wen YD, Cress WD, Roy AL, Seto E (January 2003). "Histone deacetylase 3 binds to and regulates the multifunctional transcription factor TFII-I". J. Biol. Chem. 278 (3): 1841–7. doi:10.1074/jbc.M206528200. PMID 12393887.
  31. ^ Tussié-Luna MI, Bayarsaihan D, Seto E, Ruddle FH, Roy AL (October 2002). "Physical and functional interactions of histone deacetylase 3 with TFII-I family proteins and PIASxbeta". Proc. Natl. Acad. Sci. U.S.A. 99 (20): 12807–12. Bibcode:2002PNAS...9912807T. doi:10.1073/pnas.192464499. PMC 130541. PMID 12239342.
  32. ^ a b c 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". J. Biol. Chem. 276 (38): 35826–35. doi:10.1074/jbc.M104935200. PMID 11466315.
  33. ^ a b Grozinger CM, Hassig CA, Schreiber SL (April 1999). "Three proteins define a class of human histone deacetylases related to yeast Hda1p". Proc. Natl. Acad. Sci. U.S.A. 96 (9): 4868–73. Bibcode:1999PNAS...96.4868G. doi:10.1073/pnas.96.9.4868. PMC 21783. PMID 10220385.
  34. ^ a b c d 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". Mol. Cell. 9 (1): 45–57. doi:10.1016/S1097-2765(01)00429-4. hdl:11858/00-001M-0000-002C-9FF9-9. PMID 11804585.
  35. ^ a b Grozinger CM, Schreiber SL (July 2000). "Regulation of histone deacetylase 4 and 5 and transcriptional activity by 14-3-3-dependent cellular localization". Proc. Natl. Acad. Sci. U.S.A. 97 (14): 7835–40. Bibcode:2000PNAS...97.7835G. doi:10.1073/pnas.140199597. PMC 16631. PMID 10869435.
  36. ^ Petrie K, Guidez F, Howell L, Healy L, Waxman S, Greaves M, Zelent A (May 2003). "The histone deacetylase 9 gene encodes multiple protein isoforms". J. Biol. Chem. 278 (18): 16059–72. doi:10.1074/jbc.M212935200. PMID 12590135.
  37. ^ Zhou X, Richon VM, Rifkind RA, Marks PA (February 2000). "Identification of a transcriptional repressor related to the noncatalytic domain of histone deacetylases 4 and 5". Proc. Natl. Acad. Sci. U.S.A. 97 (3): 1056–61. Bibcode:2000PNAS...97.1056Z. doi:10.1073/pnas.97.3.1056. PMC 15519. PMID 10655483.
  38. ^ Baek SH, Ohgi KA, Rose DW, Koo EH, Glass CK, Rosenfeld MG (July 2002). "Exchange of N-CoR corepressor and Tip60 coactivator complexes links gene expression by NF-kappaB and beta-amyloid precursor protein". Cell. 110 (1): 55–67. doi:10.1016/S0092-8674(02)00809-7. PMID 12150997. S2CID 17679498.
  39. ^ Mahlknecht U, Will J, Varin A, Hoelzer D, Herbein G (September 2004). "Histone deacetylase 3, a class I histone deacetylase, suppresses MAPK11-mediated activating transcription factor-2 activation and represses TNF gene expression". J. Immunol. 173 (6): 3979–90. doi:10.4049/jimmunol.173.6.3979. PMID 15356147.
  40. ^ a b c Yoon HG, Chan DW, Reynolds AB, Qin J, Wong J (September 2003). "N-CoR mediates DNA methylation-dependent repression through a methyl CpG binding protein Kaiso". Mol. Cell. 12 (3): 723–34. doi:10.1016/j.molcel.2003.08.008. PMID 14527417.
  41. ^ a b Yoon HG, Chan DW, Huang ZQ, Li J, Fondell JD, Qin J, Wong J (March 2003). "Purification and functional characterization of the human N-CoR complex: the roles of HDAC3, TBL1 and TBLR1". EMBO J. 22 (6): 1336–46. doi:10.1093/emboj/cdg120. PMC 151047. PMID 12628926.
  42. ^ a b 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". EMBO J. 19 (16): 4342–50. doi:10.1093/emboj/19.16.4342. PMC 302030. PMID 10944117.
  43. ^ a b Underhill C, Qutob MS, Yee SP, Torchia J (December 2000). "A novel nuclear receptor corepressor complex, N-CoR, contains components of the mammalian SWI/SNF complex and the corepressor KAP-1". J. Biol. Chem. 275 (51): 40463–70. doi:10.1074/jbc.M007864200. PMID 11013263.
  44. ^ a b Guenther MG, Lane WS, Fischle W, Verdin E, Lazar MA, Shiekhattar R (May 2000). "A core SMRT corepressor complex containing HDAC3 and TBL1, a WD40-repeat protein linked to deafness". Genes Dev. 14 (9): 1048–57. doi:10.1101/gad.14.9.1048. PMC 316569. PMID 10809664.
  45. ^ a b Guenther MG, Yu J, Kao GD, Yen TJ, Lazar MA (December 2002). "Assembly of the SMRT-histone deacetylase 3 repression complex requires the TCP-1 ring complex". Genes Dev. 16 (24): 3130–5. doi:10.1101/gad.1037502. PMC 187500. PMID 12502735.
  46. ^ a b c Franco PJ, Li G, Wei LN (August 2003). "Interaction of nuclear receptor zinc finger DNA binding domains with histone deacetylase". Mol. Cell. Endocrinol. 206 (1–2): 1–12. doi:10.1016/S0303-7207(03)00254-5. PMID 12943985. S2CID 19487189.
  47. ^ Shi Y, Hon M, Evans RM (March 2002). "The peroxisome proliferator-activated receptor delta, an integrator of transcriptional repression and nuclear receptor signaling". Proc. Natl. Acad. Sci. U.S.A. 99 (5): 2613–8. Bibcode:2002PNAS...99.2613S. doi:10.1073/pnas.052707099. PMC 122396. PMID 11867749.
  48. ^ a b Fajas L, Egler V, Reiter R, Hansen J, Kristiansen K, Debril MB, Miard S, Auwerx J (December 2002). "The retinoblastoma-histone deacetylase 3 complex inhibits PPARgamma and adipocyte differentiation". Dev. Cell. 3 (6): 903–10. doi:10.1016/S1534-5807(02)00360-X. PMID 12479814.
  49. ^ Wu WS, Vallian S, Seto E, Yang WM, Edmondson D, Roth S, Chang KS (April 2001). "The growth suppressor PML represses transcription by functionally and physically interacting with histone deacetylases". Mol. Cell. Biol. 21 (7): 2259–68. doi:10.1128/MCB.21.7.2259-2268.2001. PMC 86860. PMID 11259576.
  50. ^ Nicolas E, Ait-Si-Ali S, Trouche D (August 2001). "The histone deacetylase HDAC3 targets RbAp48 to the retinoblastoma protein". Nucleic Acids Res. 29 (15): 3131–6. doi:10.1093/nar/29.15.3131. PMC 55834. PMID 11470869.
  51. ^ Fischle W, Verdin E, Greene WC (August 2001). "Duration of nuclear NF-kappaB action regulated by reversible acetylation". Science. 293 (5535): 1653–7. Bibcode:2001Sci...293.1653C. doi:10.1126/science.1062374. hdl:11858/00-001M-0000-002C-9FF1-A. PMID 11533489. S2CID 45796404.
  52. ^ Lai A, Lee JM, Yang WM, DeCaprio JA, Kaelin WG, Seto E, Branton PE (October 1999). "RBP1 recruits both histone deacetylase-dependent and -independent repression activities to retinoblastoma family proteins". Mol. Cell. Biol. 19 (10): 6632–41. doi:10.1128/mcb.19.10.6632. PMC 84642. PMID 10490602.
  53. ^ Schroeder TM, Kahler RA, Li X, Westendorf JJ (October 2004). "Histone deacetylase 3 interacts with runx2 to repress the osteocalcin promoter and regulate osteoblast differentiation". J. Biol. Chem. 279 (40): 41998–2007. doi:10.1074/jbc.M403702200. PMID 15292260.
  54. ^ Vaute O, Nicolas E, Vandel L, Trouche D (January 2002). "Functional and physical interaction between the histone methyl transferase Suv39H1 and histone deacetylases". Nucleic Acids Res. 30 (2): 475–81. doi:10.1093/nar/30.2.475. PMC 99834. PMID 11788710.
  55. ^ Li G, Franco PJ, Wei LN (October 2003). "Identification of histone deacetylase-3 domains that interact with the orphan nuclear receptor TR2". Biochem. Biophys. Res. Commun. 310 (2): 384–90. doi:10.1016/j.bbrc.2003.08.145. PMID 14521922.
  56. ^ 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". Mol. Endocrinol. 15 (8): 1318–28. doi:10.1210/mend.15.8.0682. PMID 11463856.
  57. ^ Tan F, Lu L, Cai Y, Wang J, Xie Y, Wang L, Gong Y, Xu BE, Wu J, Luo Y, Qiang B, Yuan J, Sun X, Peng X (July 2008). "Proteomic analysis of ubiquitinated proteins in normal hepatocyte cell line Chang liver cells". Proteomics. 8 (14): 2885–96. doi:10.1002/pmic.200700887. PMID 18655026. S2CID 25586938.
  58. ^ Yang WM, Yao YL, Sun JM, Davie JR, Seto E (October 1997). "Isolation and characterization of cDNAs corresponding to an additional member of the human histone deacetylase gene family". J. Biol. Chem. 272 (44): 28001–7. doi:10.1074/jbc.272.44.28001. PMID 9346952.
  59. ^ Yao YL, Yang WM, Seto E (September 2001). "Regulation of transcription factor YY1 by acetylation and deacetylation". Mol. Cell. Biol. 21 (17): 5979–91. doi:10.1128/MCB.21.17.5979-5991.2001. PMC 87316. PMID 11486036.

Further reading[edit]

External links[edit]

This article incorporates text from the United States National Library of Medicine, which is in the public domain.