![[Feedback]](/icons/banner/feedbackACT.gif){kind=icon}
![[For Subscribers]](/icons/banner/subscriberACT.gif){kind=icon}
![[Archive]](/icons/banner/archiveACT.gif){kind=icon}
![[Search]](/icons/banner/searchACT.gif){kind=icon}
![[Contents]](/icons/banner/tocACT.gif){kind=icon}
|
|
|
|
|
||
Manitoba Institute of Cell Biology, Winnipeg, Manitoba, Canada
3 To whom correspondence should be addressed. E-mail: davie{at}cc.umanitoba.ca.
This article reviews the effects of the short-chain fatty acid butyrate on histone deacetylase (HDAC) activity. Sodium butyrate has multiple effects on cultured mammalian cells that include inhibition of proliferation, induction of differentiation and induction or repression of gene expression. The observation that butyrate treatment of cells results in histone hyperacetylation initiated a flurry of activity that led to the discovery that butyrate inhibits HDAC activity. Butyrate has been an essential agent for determining the role of histone acetylation in chromatin structure and function. Interestingly, inhibition of HDAC activity affects the expression of only 2% of mammalian genes. Promoters of butyrate-responsive genes have butyrate response elements, and the action of butyrate is often mediated through Sp1/Sp3 binding sites (e.g., p21Waf1/Cip1). We demonstrated that Sp1 and Sp3 recruit HDAC1 and HDAC2, with the latter being phosphorylated by protein kinase CK2. A model is proposed in which inhibition of Sp1/Sp3–associated HDAC activity leads to histone hyperacetylation and transcriptional activation of the p21Waf1/Cip1 gene; p21Waf1/Cip1 inhibits cyclin-dependent kinase 2 activity and thereby arrests cell cycling. Pending the cell background, the nonproliferating cells may enter differentiation or apoptotic pathways. The potential of butyrate and HDAC inhibitors in the prevention and treatment of cancer is presented.
KEY WORDS: • sodium butyrate • histone deacetylase • p21Waf1/Cip1 • histone acetylation • gene expression • Sp1 • Sp3
This article has been cited by other articles:
|
|
 |
|
  D. M. Bond, E. S. Dennis, B. J. Pogson, and E. J. Finnegan Histone Acetylation, VERNALIZATION INSENSITIVE 3, FLOWERING LOCUS C, and the Vernalization Response Mol Plant, July 1, 2009; 2(4): 724 - 737. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Z. Gao, J. Yin, J. Zhang, R. E. Ward, R. J. Martin, M. Lefevre, W. T. Cefalu, and J. Ye Butyrate Improves Insulin Sensitivity and Increases Energy Expenditure in Mice Diabetes, July 1, 2009; 58(7): 1509 - 1517. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Wang, Z. Gu, B. Heid, R. M. Akers, and H. Jiang Identification and characterization of the bovine G protein-coupled receptor GPR41 and GPR43 genes J Dairy Sci, June 1, 2009; 92(6): 2696 - 2705. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. K. Harten, D. Shukla, R. Barod, A. Hergovich, M. S. Balda, K. Matter, M. A. Esteban, and P. H. Maxwell Regulation of Renal Epithelial Tight Junctions by the von Hippel-Lindau Tumor Suppressor Gene Involves Occludin and Claudin 1 and Is Independent of E-Cadherin Mol. Biol. Cell, February 1, 2009; 20(3): 1089 - 1101. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Fukushima, Y. Aizaki, and K. Sakuma Short-Chain Fatty Acids Induce Intestinal Transient Receptor Potential Vanilloid Type 6 Expression in Rats and Caco-2 Cells J. Nutr., January 1, 2009; 139(1): 20 - 25. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 B. Zhou, T. A. Francis, H. Yang, W. Tseng, Q. Zhong, B. Frenkel, Edward. E. Morrisey, David. K. Ann, P. Minoo, E. D. Crandall, et al. GATA-6 mediates transcriptional activation of aquaporin-5 through interactions with Sp1 Am J Physiol Cell Physiol, November 1, 2008; 295(5): C1141 - C1150. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. Haumaitre, O. Lenoir, and R. Scharfmann Histone Deacetylase Inhibitors Modify Pancreatic Cell Fate Determination and Amplify Endocrine Progenitors Mol. Cell. Biol., October 15, 2008; 28(20): 6373 - 6383. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. Lecona, J. I. Barrasa, N. Olmo, B. Llorente, J. Turnay, and M. A. Lizarbe Upregulation of Annexin A1 Expression by Butyrate in Human Colon Adenocarcinoma Cells: Role of p53, NF-Y, and p38 Mitogen-Activated Protein Kinase Mol. Cell. Biol., August 1, 2008; 28(15): 4665 - 4674. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. L. Kien and R. Blauwiekel Cecal Infusion of Butyrate Does Not Alter Cecal Concentration of Butyrate in Piglets Fed Inulin JPEN J Parenter Enteral Nutr, July 1, 2008; 32(4): 439 - 442. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H.-H. Lee, S.-S. Chang, S.-J. Lin, H.-H. Chua, T.-J. Tsai, K. Tsai, Y.-C. Lo, H.-C. Chen, and C.-H. Tsai Essential role of PKC{delta} in histone deacetylase inhibitor-induced Epstein-Barr virus reactivation in nasopharyngeal carcinoma cells J. Gen. Virol., April 1, 2008; 89(4): 878 - 883. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. L. Kien, C. P. Peltier, S. Mandal, J. R. Davie, and R. Blauwiekel Effects of the In Vivo Supply of Butyrate on Histone Acetylation of Cecum in Piglets JPEN J Parenter Enteral Nutr, January 1, 2008; 32(1): 51 - 56. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. Haarmann-Stemmann, H. Bothe, A. Kohli, U. Sydlik, J. Abel, and E. Fritsche Analysis of the Transcriptional Regulation and Molecular Function of the Aryl Hydrocarbon Receptor Repressor in Human Cell Lines Drug Metab. Dispos., December 1, 2007; 35(12): 2262 - 2269. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
I. R. Sanderson Dietary Modulation of GALT J. Nutr., November 1, 2007; 137(11): 2557S - 2562S. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 F. Di Renzo, M. L. Broccia, E. Giavini, and E. Menegola Relationship between Embryonic Histonic Hyperacetylation and Axial Skeletal Defects in Mouse Exposed to the Three HDAC Inhibitors Apicidin, MS-275, and Sodium Butyrate Toxicol. Sci., August 1, 2007; 98(2): 582 - 588. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Rada-Iglesias, S. Enroth, A. Ameur, C. M. Koch, G. K. Clelland, P. Respuela-Alonso, S. Wilcox, O. M. Dovey, P. D. Ellis, C. F. Langford, et al. Butyrate mediates decrease of histone acetylation centered on transcription start sites and down-regulation of associated genes Genome Res., June 1, 2007; 17(6): 708 - 719. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. L. Morris, R. R. Arnold, and J. Webster-Cyriaque Signaling Cascades Triggered by Bacterial Metabolic End Products during Reactivation of Kaposi's Sarcoma-Associated Herpesvirus J. Virol., June 1, 2007; 81(11): 6032 - 6042. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. L. Kien, R. Blauwiekel, C. H. Williams, J. Y. Bunn, and R. K. Buddington Lactulose Feeding Lowers Cecal Densities of Clostridia in Piglets JPEN J Parenter Enteral Nutr, May 1, 2007; 31(3): 194 - 198. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. Plata, C. R. Sussman, A. Sindic, J. O. Liang, D. B. Mount, Z. M. Josephs, M.-H. Chang, and M. F. Romero Zebrafish Slc5a12 Encodes an Electroneutral Sodium Monocarboxylate Transporter (SMCTn): A COMPARISON WITH THE ELECTROGENIC SMCT (SMCTe/Slc5a8) J. Biol. Chem., April 20, 2007; 282(16): 11996 - 12009. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. M. Almeida, Y. Murakami, A. Baker, Y. Maeda, I. A.G. Roberts, T. Kinoshita, D. M. Layton, and A. Karadimitris Targeted Therapy for Inherited GPI Deficiency N. Engl. J. Med., April 19, 2007; 356(16): 1641 - 1647. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. L. Kien, R. Blauwiekel, J. Y. Bunn, T. L. Jetton, W. L. Frankel, and J. J. Holst Cecal Infusion of Butyrate Increases Intestinal Cell Proliferation in Piglets J. Nutr., April 1, 2007; 137(4): 916 - 922. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. J. Mosley, K. N. Meekings, C. McCarthy, D. Shepherd, V. Cerundolo, R. Mazitschek, Y. Tanaka, G. P. Taylor, and C. R. Bangham Histone deacetylase inhibitors increase virus gene expression but decrease CD8+ cell antiviral function in HTLV-1 infection Blood, December 1, 2006; 108(12): 3801 - 3807. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. C. Roy, C. L. Kien, L. Bouthillier, and E. Levy Short-Chain Fatty Acids: Ready for Prime Time? Nutr Clin Pract, August 1, 2006; 21(4): 351 - 366. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. L. Kien, M. Schmitz-Brown, T. Solley, D. Sun, and W. L. Frankel Increased Colonic Luminal Synthesis of Butyric Acid Is Associated with Lowered Colonic Cell Proliferation in Piglets J. Nutr., January 1, 2006; 136(1): 64 - 69. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
X. Tong, L. Yin, S. Joshi, D. W. Rosenberg, and C. Giardina Cyclooxygenase-2 Regulation in Colon Cancer Cells: MODULATION OF RNA POLYMERASE II ELONGATION BY HISTONE DEACETYLASE INHIBITORS J. Biol. Chem., April 22, 2005; 280(16): 15503 - 15509. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. Gondcaille, M. Depreter, S. Fourcade, M. R. Lecca, S. Leclercq, P. G.P. Martin, T. Pineau, F. Cadepond, M. ElEtr, N. Bertrand, et al. Phenylbutyrate up-regulates the adrenoleukodystrophy-related gene as a nonclassical peroxisome proliferator J. Cell Biol., April 11, 2005; 169(1): 93 - 104. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Ye, D. Shedd, and G. Miller An Sp1 Response Element in the Kaposi's Sarcoma-Associated Herpesvirus Open Reading Frame 50 Promoter Mediates Lytic Cycle Induction by Butyrate J. Virol., February 1, 2005; 79(3): 1397 - 1408. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Nevels, C. Paulus, and T. Shenk Human cytomegalovirus immediate-early 1 protein facilitates viral replication by antagonizing histone deacetylation PNAS, December 7, 2004; 101(49): 17234 - 17239. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
I. R. Sanderson Short Chain Fatty Acid Regulation of Signaling Genes Expressed by the Intestinal Epithelium J. Nutr., September 1, 2004; 134(9): 2450S - 2454S. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. Klampfer, J. Huang, L.-A. Swaby, and L. Augenlicht Requirement of Histone Deacetylase Activity for Signaling by STAT1 J. Biol. Chem., July 16, 2004; 279(29): 30358 - 30368. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 N. Druesne, A. Pagniez, C. Mayeur, M. Thomas, C. Cherbuy, P.-H. Duee, P. Martel, and C. Chaumontet Diallyl disulfide (DADS) increases histone acetylation and p21waf1/cip1 expression in human colon tumor cell lines Carcinogenesis, July 1, 2004; 25(7): 1227 - 1236. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y.-D. Wei, K. Tepperman, M.-y. Huang, M. A. Sartor, and A. Puga Chromium Inhibits Transcription from Polycyclic Aromatic Hydrocarbon-inducible Promoters by Blocking the Release of Histone Deacetylase and Preventing the Binding of p300 to Chromatin J. Biol. Chem., February 6, 2004; 279(6): 4110 - 4119. [Abstract] [Full Text] [PDF]
|
|
