HD CAG-correlated gene expression changes support a simple dominant gain of function

Human Molecular Genetics

Volumn 20, Issue 14, 2011, Pages 2846-2860

  Jacobsen, Jessie C ^a   Gregory, Gillian C ^a   Woda, Juliana M ^a,f   Thompson, Morgan N ^a   Coser, Kathryn R ^b   Murthy, Vidya ^a   Kohane, Isaac S ^c,d,e   Gusella, James F ^a   Seong, Ihn Sik ^a   MacDonald, Marcy E ^a   Shioda, Toshi ^b   Lee, Jong Min ^a  

^a MASSACHUSETTS GENERAL HOSPITAL   (United States)

^b MASSACHUSETTS GENERAL HOSPITAL CANCER CENTER   (United States)

^c BOSTON CHILDREN S HOSPITAL   (United States)

^d Harvard Medical School Center for Biomedical Informatics   (United States)

^e I2b2 National Center for Biomedical Computing   (United States)

^f ATHERSYS INC   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

HUNTINGTIN; LIPID; LIPOPROTEIN; STEROL;

ALLELE; ANIMAL EXPERIMENT; ANIMAL MODEL; ARTICLE; CAG REPEAT; CONTROLLED STUDY; EMBRYONIC STEM CELL; ENERGY METABOLISM; GENE CLUSTER; GENE EXPRESSION; GENE FUNCTION; GENE SILENCING; HUMAN; HUMAN CELL; HUNTINGTON CHOREA; LIPID METABOLISM; MOUSE; NONHUMAN; PRIORITY JOURNAL; PROTEIN METABOLISM; WILD TYPE;

ALLELES; ANIMALS; CELL LINE; EMBRYONIC STEM CELLS; GENE EXPRESSION PROFILING; GENE EXPRESSION REGULATION; GENE KNOCK-IN TECHNIQUES; GENOME-WIDE ASSOCIATION STUDY; HUNTINGTON DISEASE; MICE; NERVE TISSUE PROTEINS; NUCLEAR PROTEINS; PEPTIDES; TRINUCLEOTIDE REPEAT EXPANSION;

EID: 79959796625     PISSN: 09646906     EISSN: 14602083     Source Type: Journal    
DOI: 10.1093/hmg/ddr195     Document Type: Article

References (54)

1. Vonsattel, J.P. and DiFiglia, M. (1998) Huntington disease. J. Neuropathol. Exp. Neurol., 57, 369-384.
2. Huntington's Disease Collaborative Research Group (1993) A novel gene containing a trinucleotide repeat that is expanded and unstable on Huntington's disease chromosomes. Cell, 72, 971-983.
3. McNeil, S.M., Novelletto, A., Srinidhi, J., Barnes, G., Kornbluth, I., Altherr, M.R., Wasmuth, J.J., Gusella, J.F., MacDonald, M.E. and Myers, R.H. (1997) Reduced penetrance of the Huntington's disease mutation. Hum. Mol. Genet., 6, 775-779.
4. Quarrell, O.W., Rigby, A.S., Barron, L., Crow, Y., Dalton, A., Dennis, N., Fryer, A.E., Heydon, F., Kinning, E., Lashwood, A. et al. (2007) Reduced penetrance alleles for Huntington's disease: a multi-centre direct observational study. J. Med. Genet., 44, e68.
5. Kenney, C., Powell, S. and Jankovic, J. (2007) Autopsy-proven Huntington's disease with 29 trinucleotide repeats. Mov. Disord., 22, 127-130.
6. Hendricks, A.E., Latourelle, J.C., Lunetta, K.L., Cupples, L.A., Wheeler, V., MacDonald, M.E., Gusella, J.F. and Myers, R.H. (2009) Estimating the probability of de novo HD cases from transmissions of expanded penetrant CAG alleles in the Huntington disease gene from male carriers of high normal alleles (27-35 CAG). Am. J. Med. Genet. A., 149A, 1375-1381.
7. Duyao, M., Ambrose, C., Myers, R., Novelletto, A., Persichetti, F., Frontali, M., Folstein, S., Ross, C., Franz, M., Abbott, M. et al. (1993) Trinucleotide repeat length instability and age of onset in Huntington's disease. Nat. Genet., 4, 387-392.
8. Snell, R.G., MacMillan, J.C., Cheadle, J.P., Fenton, I., Lazarou, L.P., Davies, P., MacDonald, M.E., Gusella, J.F., Harper, P.S. and Shaw, D.J. (1993) Relationship between trinucleotide repeat expansion and phenotypic variation in Huntington's disease. Nat. Genet., 4, 393-397.
9. Auerbach, W., Hurlbert, M.S., Hilditch-Maguire, P., Wadghiri, Y.Z., Wheeler, V.C., Cohen, S.I., Joyner, A.L., MacDonald, M.E. and Turnbull, D.H. (2001) The HD mutation causes progressive lethal neurological disease in mice expressing reduced levels of huntingtin. Hum. Mol. Genet., 10, 2515-2523.
10. Fossale, E., Wheeler, V.C., Vrbanac, V., Lebel, L.A., Teed, A., Mysore, J.S., Gusella, J.F., MacDonald, M.E. and Persichetti, F. (2002) Identification of a presymptomatic molecular phenotype in Hdh CAG knock-in mice. Hum. Mol. Genet., 11, 2233-2241.
11. Heng, M.Y., Detloff, P.J., Paulson, H.L. and Albin, R.L. (2010) Early alterations of autophagy in Huntington disease-like mice. Autophagy, 6, 1206-1208.
12. Heng, M.Y., Tallaksen-Greene, S.J., Detloff, P.J. and Albin, R.L. (2007) Longitudinal evaluation of the Hdh(CAG)150 knock-in murine model of Huntington's disease. J. Neurosci., 27, 8989-8998.
13. Menalled, L.B. (2005) Knock-in mouse models of Huntington's disease. NeuroRx, 2, 465-470.
14. Wheeler, V.C., Auerbach, W., White, J.K., Srinidhi, J., Auerbach, A., Ryan, A., Duyao, M.P., Vrbanac, V., Weaver, M., Gusella, J.F. et al. (1999) Length-dependent gametic CAG repeat instability in the Huntington's disease knock-in mouse. Hum. Mol. Genet., 8, 115-122.
15. Wheeler, V.C., Gutekunst, C.A., Vrbanac, V., Lebel, L.A., Schilling, G., Hersch, S., Friedlander, R.M., Gusella, J.F., Vonsattel, J.P., Borchelt, D.R. et al. (2002) Early phenotypes that presage late-onset neurodegenerative disease allow testing of modifiers in Hdh CAG knock-in mice. Hum. Mol. Genet., 11, 633-640.
16. Wheeler, V.C., White, J.K., Gutekunst, C.A., Vrbanac, V., Weaver, M., Li, X.J., Li, S.H., Yi, H., Vonsattel, J.P., Gusella, J.F. et al. (2000) Long glutamine tracts cause nuclear localization of a novel form of huntingtin in medium spiny striatal neurons in HdhQ92 and HdhQ111 knock-in mice. Hum. Mol. Genet., 9, 503-513.
17. Perlis, R.H., Smoller, J.W., Mysore, J., Sun, M., Gillis, T., Purcell, S., Rietschel, M., Nothen, M.M., Witt, S., Maier, W. et al. (2010) Prevalence of incompletely penetrant Huntington's disease alleles among individuals with major depressive disorder. Am. J. Psychiatry, 167, 574-579.
18. Seong, I.S., Ivanova, E., Lee, J.M., Choo, Y.S., Fossale, E., Anderson, M., Gusella, J.F., Laramie, J.M., Myers, R.H., Lesort, M. et al. (2005) HD CAG repeat implicates a dominant property of huntingtin in mitochondrial energy metabolism. Hum. Mol. Genet., 14, 2871-2880.
19. Andrade, M.A. and Bork, P. (1995) HEAT repeats in the Huntington's disease protein. Nat. Genet., 11, 115-116.
20. Li, W., Serpell, L.C., Carter, W.J., Rubinsztein, D.C. and Huntington, J.A. (2006) Expression and characterization of full-length human huntingtin, an elongated HEAT repeat protein. J. Biol. Chem., 281, 15916-15922.
21. Seong, I.S., Woda, J.M., Song, J.J., Lloret, A., Abeyrathne, P.D., Woo, C.J., Gregory, G., Lee, J.M., Wheeler, V.C., Walz, T. et al. (2010) Huntingtin facilitates polycomb repressive complex 2. Hum. Mol. Genet., 19, 573-583.
22. Takano, H. and Gusella, J.F. (2002) The predominantly HEAT-like motif structure of huntingtin and its association and coincident nuclear entry with dorsal, an NF-kB/Rel/dorsal family transcription factor. BMC Neurosci., 3, 15.
23. Grinthal, A., Adamovic, I., Weiner, B., Karplus, M. and Kleckner, N. (2010) PR65, the HEAT-repeat scaffold of phosphatase PP2A, is an elastic connector that links force and catalysis. Proc. Natl Acad. Sci. USA, 107, 2467-2472.
24. Ambrose, C.M., Duyao, M.P., Barnes, G., Bates, G.P., Lin, C.S., Srinidhi, J., Baxendale, S., Hummerich, H., Lehrach, H., Altherr, M. et al. (1994) Structure and expression of the Huntington's disease gene: evidence against simple inactivation due to an expanded CAG repeat. Som. Cell Mol. Genet., 20, 27-38.
25. Duyao, M.P., Auerbach, A.B., Ryan, A., Persichetti, F., Barnes, G.T., McNeil, S.M., Ge, P., Vonsattel, J.P., Gusella, J.F., Joyner, A.L. et al. (1995) Inactivation of the mouse Huntington's disease gene homolog Hdh. Science, 269, 407-410.
26. Nasir, J., Floresco, S.B., O'Kusky, J.R., Diewert, V.M., Richman, J.M., Zeisler, J., Borowski, A., Marth, J.D., Phillips, A.G. and Hayden, M.R. (1995) Targeted disruption of the Huntington's disease gene results in embryonic lethality and behavioral and morphological changes in heterozygotes. Cell, 81, 811-823.
27. White, J.K., Auerbach, W., Duyao, M.P., Vonsattel, J.P., Gusella, J.F., Joyner, A.L. and MacDonald, M.E. (1997) Huntingtin is required for neurogenesis and is not impaired by the Huntington's disease CAG expansion. Nat. Genet., 17, 404-410.
28. Zeitlin, S., Liu, J.P., Chapman, D.L., Papaioannou, V.E. and Efstratiadis, A. (1995) Increased apoptosis and early embryonic lethality in mice nullizygous for the Huntington's disease gene homologue. Nat. Genet., 11, 155-163.
29. Myers, R.H., Leavitt, J., Farrer, L.A., Jagadeesh, J., McFarlane, H., Mastromauro, C.A., Mark, R.J. and Gusella, J.F. (1989) Homozygote for Huntington disease. Am. J. Hum. Genet., 45, 615-618.
30. Wexler, N.S., Young, A.B., Tanzi, R.E., Travers, H., Starosta-Rubinstein, S., Penney, J.B., Snodgrass, S.R., Shoulson, I., Gomez, F., Ramos Arroyo, M.A. et al. (1987) Homozygotes for Huntington's disease. Nature, 326, 194-197.
31. Brooks, S., Higgs, G., Jones, L. and Dunnett, S.B. (2010) Longitudinal analysis of the behavioural phenotype in Hdh((CAG)150) Huntington's disease knock-in mice. Brain Res. Bull. In press.
32. Clabough, E.B. and Zeitlin, S.O. (2006) Deletion of the triplet repeat encoding polyglutamine within the mouse Huntington's disease gene results in subtle behavioral/motor phenotypes in vivo and elevated levels of ATP with cellular senescence in vitro. Hum. Mol. Genet., 15, 607-623.
33. Zuccato, C., Belyaev, N., Conforti, P., Ooi, L., Tartari, M., Papadimou, E., MacDonald, M., Fossale, E., Zeitlin, S., Buckley, N. et al. (2007) Widespread disruption of repressor element-1 silencing transcription factor/neuron-restrictive silencer factor occupancy at its target genes in Huntington's disease. J. Neurosci., 27, 6972-6983.
34. Valenza, M., Carroll, J.B., Leoni, V., Bertram, L.N., Bjorkhem, I., Singaraja, R.R., Di Donato, S., Lutjohann, D., Hayden, M.R. and Cattaneo, E. (2007) Cholesterol biosynthesis pathway is disturbed in YAC128 mice and is modulated by huntingtin mutation. Hum. Mol. Genet., 16, 2187-2198.
35. Valenza, M., Rigamonti, D., Goffredo, D., Zuccato, C., Fenu, S., Jamot, L., Strand, A., Tarditi, A., Woodman, B., Racchi, M. et al. (2005) Dysfunction of the cholesterol biosynthetic pathway in Huntington's disease. J. Neurosci., 25, 9932-9939.
36. Zuccato, C., Tartari, M., Crotti, A., Goffredo, D., Valenza, M., Conti, L., Cataudella, T., Leavitt, B.R., Hayden, M.R., Timmusk, T. et al. (2003) Huntingtin interacts with REST/NRSF to modulate the transcription of NRSE-controlled neuronal genes. Nat. Genet., 35, 76-83.
37. Futter, M., Diekmann, H., Schoenmakers, E., Sadiq, O., Chatterjee, K. and Rubinsztein, D.C. (2009) Wild-type but not mutant huntingtin modulates the transcriptional activity of liver X receptors. J. Med. Genet., 46, 438-446.
38. Borrell-Pages, M., Zala, D., Humbert, S. and Saudou, F. (2006) Huntington's disease: from huntingtin function and dysfunction to therapeutic strategies. Cell. Mol. Life Sci., 63, 2642-2660.
39. Cattaneo, E., Rigamonti, D., Goffredo, D., Zuccato, C., Squitieri, F. and Sipione, S. (2001) Loss of normal huntingtin function: new developments in Huntington's disease research. Trends Neurosci., 24, 182-188.
40. Zuccato, C., Ciammola, A., Rigamonti, D., Leavitt, B.R., Goffredo, D., Conti, L., MacDonald, M.E., Friedlander, R.M., Silani, V., Hayden, M.R. et al. (2001) Loss of huntingtin-mediated BDNF gene transcription in Huntington's disease. Science, 293, 493-498.
41. MacDonald, M.E. (2003) Huntingtin: alive and well and working in middle management. Sci. STKE, 2003, pe48.
42. Caviston, J.P. and Holzbaur, E.L. (2009) Huntingtin as an essential integrator of intracellular vesicular trafficking. Trends Cell. Biol., 19, 147-155.
43. Faber, P.W., Barnes, G.T., Srinidhi, J., Chen, J., Gusella, J.F. and MacDonald, M.E. (1998) Huntingtin interacts with a family of WW domain proteins. Hum. Mol. Genet., 7, 1463-1474.
44. Godin, J.D., Colombo, K., Molina-Calavita, M., Keryer, G., Zala, D., Charrin, B.C., Dietrich, P., Volvert, M.L., Guillemot, F., Dragatsis, I. et al. (2010) Huntingtin is required for mitotic spindle orientation and mammalian neurogenesis. Neuron, 67, 392-406.
45. Hilditch-Maguire, P., Trettel, F., Passani, L.A., Auerbach, A., Persichetti, F. and MacDonald, M.E. (2000) Huntingtin: an iron-regulated protein essential for normal nuclear and perinuclear organelles. Hum. Mol. Genet., 9, 2789-2797.
46. Kegel, K.B., Sapp, E., Alexander, J., Valencia, A., Reeves, P., Li, X., Masso, N., Sobin, L., Aronin, N. and DiFiglia, M. (2009) Polyglutamine expansion in huntingtin alters its interaction with phospholipids. J. Neurochem., 110, 1585-1597.
47. Lumsden, A.L., Henshall, T.L., Dayan, S., Lardelli, M.T. and Richards, R.I. (2007) Huntingtin-deficient zebrafish exhibit defects in iron utilization and development. Hum. Mol. Genet., 16, 1905-1920.
48. Truant, R., Atwal, R.S. and Burtnik, A. (2007) Nucleocytoplasmic trafficking and transcription effects of huntingtin in Huntington's disease. Prog. Neurobiol., 83, 211-227.
49. Valencia, A., Reeves, P.B., Sapp, E., Li, X., Alexander, J., Kegel, K.B., Chase, K., Aronin, N. and DiFiglia, M. (2010) Mutant huntingtin and glycogen synthase kinase 3-beta accumulate in neuronal lipid rafts of a presymptomatic knock-in mouse model of Huntington's disease. J. Neurosci. Res., 88, 179-190.
50. Zhang, H., Das, S., Li, Q.Z., Dragatsis, I., Repa, J., Zeitlin, S., Hajnoczky, G. and Bezprozvanny, I. (2008) Elucidating a normal function of huntingtin by functional and microarray analysis of huntingtin-null mouse embryonic fibroblasts. BMC Neurosci., 9, 38.
51. Battista, N., Bari, M., Tarditi, A., Mariotti, C., Bachoud-Levi, A.C., Zuccato, C., Finazzi-Agro, A., Genitrini, S., Peschanski, M., Di Donato, S. et al. (2007) Severe deficiency of the fatty acid amide hydrolase (FAAH) activity segregates with the Huntington's disease mutation in peripheral lymphocytes. Neurobiol. Dis., 27, 108-116.
52. Gines, S., Seong, I.S., Fossale, E., Ivanova, E., Trettel, F., Gusella, J.F., Wheeler, V.C., Persichetti, F. and MacDonald, M.E. (2003) Specific progressive cAMP reduction implicates energy deficit in presymptomatic Huntington's disease knock-in mice. Hum. Mol. Genet., 12, 497-508.
53. Subramanian, A., Tamayo, P., Mootha, V.K., Mukherjee, S., Ebert, B.L., Gillette, M.A., Paulovich, A., Pomeroy, S.L., Golub, T.R., Lander, E.S. et al. (2005) Gene set enrichment analysis: a knowledge-based approach for interpreting genome-wide expression profiles. Proc. Natl Acad. Sci. USA, 102, 15545-15550.
54. Tian, L., Greenberg, S.A., Kong, S.W., Altschuler, J., Kohane, I.S. and Park, P.J. (2005) Discovering statistically significant pathways in expression profiling studies. Proc. Natl. Acad. Sci. USA, 102, 13544-13549.