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SAMPLES (8)
mace:id
Technology # Array version
# SEVERAL # # SEVERAL
Affymetrix # HGU 133 Plus 2
Affymetrix # MGU 74 Av2
Affymetrix # MoGene V1.0st
Affymetrix # Mouse 430A
Affymetrix # Rhesus
Agilent # AGHUMAN
Agilent # AGMOUSE
Applied Biosystems # HGS V1
Applied Biosystems # HGS V2
Applied Biosystems # MGS V1
Applied Biosystems # MGS V2
Applied Biosystems # RGS V1
Genopole SXB # SXBH1
Genopole SXB # SXBH2
Genopole SXB # SXBH3
Genopole SXB # SXBM1
Genopole SXB # SXBM2
Genopole SXB # SXBM3
Illumina # HumanHT-12 V4.0
Illumina # HUMANWG6v3
Illumina # MouseWG-6 v2.0
Species
# SEVERAL
Cercocebus atys
Chlorocebus sabaeus
Homo sapiens
Macaca mulatta
Macaca Nemestrina
Mus musculus
Pan troglodytes
Rattus norvegicus
Organ
# OTHER
# SEVERAL
Adenoid
Adrenal gland
Bladder
Blood
Blood vessel
Brain
Bronchi
Cervix
Embryo
Esophagus
Gallblader
Heart
Hypotalamus
Intestine
Kidney
Larynx
Liver
Lung
Lymph node
Mammary gland
Mussle
Pancreas
Parathyroid
Penis
Pharynx
Pineal gland
Pituitary gland
Prostate
Salivary gland
Seminal vesicle
Skin
Spinal cord
Spleen
Stomach
Test
Thymus
Thyroid
Tonsil
Trachea
Ureter
Uterus
Vagina
Vas deferens
Tissue
# OTHER
# SEVERAL
Bone Marrow
Connective - Dense Irregular Tissue (Collagen)
Connective - Dense Regular Tissue (Collagen)
Connective - Dense Regular Tissue (Elastic)
Connective - Loose Tissue (Adipose)
Connective - Loose Tissue (Areolar)
Connective - Loose Tissue (Reticular)
Epithelium - Simple (Columnar)
Epithelium - Simple (Cuboidal)
Epithelium - Simple (Pseudostratified)
Epithelium - Simple (Squamous)
Epithelium - Stratified (Columnar / Cuboidal)
Epithelium - Stratified (Squamous: Keratinized)
Epithelium - Stratified (Squamous: NonKeratinized)
Fluid - Blood
Fluid - Lymph
Gland - Endocrine Glands
Gland - Exocrine Glands (Ducts and Tubules)
Muscle - Non-striated
Muscle - Striated (Cardiac)
Muscle - Striated (Skeletal)
Nervous - Nerves
Nervous - Neurons (Bipolar)
Nervous - Neurons (Multipolar)
Nervous - Neurons (Unipolar)
Nervous - Receptors
Placenta
Stem cells
Supportive - Cartilage (Elastic)
Supportive - Cartilage (Fibrocartilage)
Supportive - Cartilage (Hyaline)
Supportive - Osseous (Compact)
Supportive - Osseous (Spongey)
Physiopathology
# HEALTHY
# OTHER
# SEVERAL
apoptosis
autocrine signaling
differentiation
drug response
electric response
endocrine signaling
environemental response
homeostasis
immune response
mechanic response
necrosis
paracrine signaling
proliferation
Type
# OTHER
# SEVERAL
conditional knockout
drug stress
electric stress
environmental stress
ground state
immune stress
knockdown RNAi
knockout
mechanic stress
stable transfection
time course
transient transfection
Name
Attached file
download project data file ('.map')
Attached file (see:
ruid website
)
download project data file ('.map' RUID converted)
Attached file
download raw data files ('.zip')
Attached file
download annotation files ('.zip')
User name
Sebastian Eilebrecht
Email
eilebrecht@ihes.fr
Phone / Fax number
+491755662397 /
Location
IHES (Systems Epigenomics Group) - 35, route de Chartres - 91440 Bures sur Yvette, France
Scientific description
The small nuclear 7SK RNA negatively controls transcription by inactivating positive transcription elongation factor b (P-TEFb) and is an integral component of TAT-dependent and independent HIV-1 transcription initiation complexes. 7SK RNA has recently been shown to also directly control HMGA1 transcription activity. HMGA1 is a master regulator of gene expression and its deregulation is associated with virtually any type of human cancer. The degree of HMGA1 overexpression thereby correlates with tumor malignancy and metastatic potential. 7SK snRNA directly interacts through its loop 2 (7SK L2) with the first A/T DNA binding hook of HMGA1. We have developed several 7SK L2 RNA chimera with the Epstein Barr Virus expressed RNA 2 (EBER2) to target HMGA1 function in transcription regulation. The efficiency of interfering with HMGA1 transcription activity by the chimeric 7SK L2 — EBER2 fusions by large exceeds the efficiency of 7SK wild-type RNA due to the stronger EBER2 promoter activity. Furthermore, the 7SK L2 — EBER2 chimera do not interfere with P-TEFb controlled transcription elongation or the formation of 7SK sn/hnRNPs. The comparison of the effects of wild-type 7SK RNA on cellular transcriptome dynamics with those induced by the two 7SK L2 mutants as well as the changes in gene expression following inhibition of HMGA1 allow the identification and characterization of HMGA1-dependent and independent effects of 7SK snRNA. We furthermore also present evidence for P-TEFb and HMGA1-independent 7SK RNA L2 regulatory activity.
Technical description
For microarray analyses, RNA amplification, labeling, hybridization and detection were performed following the protocols supplied by Applied Biosystems using the corresponding kits (Applied Biosystems, ProdNo: 4339628 and 4336875). The data obtained were analyzed as described previously (10, 41,46-49). The statistical analysis of the transcriptome data has been described previously (10, 41). Gene ontology enrichment analyses were also described previously (41, 49). The signalosome network inference will be described in detail elsewhere (Bécavin et al. in preparation), and the network representation tool used was Cytoscape (51). References: 1. Matera, A.G. and Ward, D.C. (1993) Nucleoplasmic organization of small nuclear ribonucleoproteins in cultured human cells. J Cell Biol, 121, 715-727. 2. Gurney, T., Jr. and Eliceiri, G.L. (1980) Intracellular distribution of low molecular weight RNA species in HeLa cells. J Cell Biol, 87, 398-403. 3. Zieve, G., Benecke, B.J. and Penman, S. (1977) Synthesis of two classes of small RNA species in vivo and in vitro. Biochemistry, 16, 4520-4525. 4. Zieve, G. and Penman, S. (1976) Small RNA species of the HeLa cell: metabolism and subcellular localization. Cell, 8, 19-31. 5. Nguyen, V.T., Kiss, T., Michels, A.A. and Bensaude, O. (2001) 7SK small nuclear RNA binds to and inhibits the activity of CDK9/cyclin T complexes. Nature, 414, 322-325. 6. Yang, Z., Zhu, Q., Luo, K. and Zhou, Q. (2001) The 7SK small nuclear RNA inhibits the CDK9/cyclin T1 kinase to control transcription. Nature, 414, 317-322. 7. Barboric, M. and Lenasi, T. Kick-sTARting HIV-1 transcription elongation by 7SK snRNP deporTATion. Nat Struct Mol Biol, 17, 928-930. 8. D'Orso, I. and Frankel, A.D. RNA-mediated displacement of an inhibitory snRNP complex activates transcription elongation. Nat Struct Mol Biol, 17, 815-821. 9. Cho, W.K., Jang, M.K., Huang, K., Pise-Masison, C.A. and Brady, J.N. Human T-Lymphotropic Virus Type 1 Tax Protein Complexes with P-TEFb and Competes for Brd4 and 7SK snRNP/HEXIM1 Binding. J Virol. 10. Eilebrecht, S., Brysbaert, G., Wegert, T., Urlaub, H., Benecke, B.-J. and Benecke,A. (2010) 7SK small nuclear RNA is a direct affector of HMGA1 function in transcription regulation. Nucleic Acids Research. 11. Egloff, S., Van Herreweghe, E. and Kiss, T. (2006) Regulation of polymerase II transcription by 7SK snRNA: two distinct RNA elements direct P-TEFb and HEXIM1 binding. Mol Cell Biol, 26, 630-642. 12. Van Herreweghe, E., Egloff, S., Goiffon, I., Jady, B.E., Froment, C., Monsarrat, B. and Kiss, T. (2007) Dynamic remodelling of human 7SK snRNP controls the nuclear level of active P-TEFb. EMBO J, 26, 3570-3580. 13. Reeves, R. (2001) Molecular biology of HMGA proteins: hubs of nuclear function. Gene, 277, 63-81. 14. Reeves, R. (2003) HMGA proteins: flexibility finds a nuclear niche? Biochem Cell Biol, 81, 185-195. 15. Reeves, R. (2004) HMGA proteins: isolation, biochemical modifications, and nucleosome interactions. Methods Enzymol, 375, 297-322. 16. Reeves, R. and Beckerbauer, L. (2001) HMGI/Y proteins: flexible regulators of transcription and chromatin structure. Biochim Biophys Acta, 1519, 13-29. 17. Chiappetta, G., Avantaggiato, V., Visconti, R., Fedele, M., Battista, S., Trapasso, F., Merciai, B.M., Fidanza, V., Giancotti, V., Santoro, M. et al. (1996) High level expression of the HMGI (Y) gene during embryonic development. Oncogene, 13, 2439-2446. 18. Chiappetta, G., Bandiera, A., Berlingieri, M.T., Visconti, R., Manfioletti, G., Battista, S., Martinez-Tello, F.J., Santoro, M., Giancotti, V. and Fusco, A. (1995) The expression of the high mobility group HMGI (Y) proteins correlates with the malignant phenotype of human thyroid neoplasias. Oncogene, 10, 1307-1314. 19. Cleynen, I. and Van de Ven, W.J. (2008) The HMGA proteins: a myriad of functions (Review). Int J Oncol, 32, 289-305. 20. Fusco, A. and Fedele, M. (2007) Roles of HMGA proteins in cancer. Nat Rev Cancer, 7, 899-910. 21. Hess, J.L. (1998) Chromosomal translocations in benign tumors: the HMGI proteins. Am J Clin Pathol, 109, 251-261. 22. Reeves, R. and Beckerbauer, L.M. (2003) HMGA proteins as therapeutic drug targets. Prog Cell Cycle Res, 5, 279-286. 23. Himes, S.R., Reeves, R., Attema, J., Nissen, M., Li, Y. and Shannon, M.F. (2000) The role of high-mobility group I(Y) proteins in expression of IL-2 and T cell proliferation. J Immunol, 164, 3157-3168. 24. John, S., Reeves, R.B., Lin, J.X., Child, R., Leiden, J.M., Thompson, C.B. and Leonard, W.J. (1995) Regulation of cell-type-specific interleukin-2 receptor alpha-chain gene expression: potential role of physical interactions between Elf-1, HMG-I(Y), and NF-kappa B family proteins. Mol Cell Biol, 15, 1786-1796. 25. John, S., Robbins, C.M. and Leonard, W.J. (1996) An IL-2 response element in the human IL-2 receptor alpha chain promoter is a composite element that binds Stat5, Elf-1, HMG-I(Y) and a GATA family protein. EMBO J, 15, 5627-5635. 26. Lehn, D.A., Elton, T.S., Johnson, K.R. and Reeves, R. (1988) A conformational study of the sequence specific binding of HMG-I (Y) with the bovine interleukin-2 cDNA. Biochem Int, 16, 963-971. 27. Magnuson, N.S., Spies, A.G., Nissen, M.S., Buck, C.D., Weinberg, A.D., Barr, P.J., Magnuson, J.A. and Reeves, R. (1987) Bovine interleukin 2: regulatory mechanisms. Vet Immunol Immunopathol, 17, 183-192. 28. Reeves, R., Elton, T.S., Nissen, M.S., Lehn, D. and Johnson, K.R. (1987) Posttranscriptional gene regulation and specific binding of the nonhistone protein HMG-I by the 3' untranslated region of bovine interleukin 2 cDNA. Proc Natl Acad Sci U S A, 84, 6531-6535. 29. Reeves, R., Leonard, W.J. and Nissen, M.S. (2000) Binding of HMG-I(Y) imparts architectural specificity to a positioned nucleosome on the promoter of the human interleukin-2 receptor alpha gene. Mol Cell Biol, 20, 4666-4679. 30. Danzeiser, D.A., Urso, O. and Kunkel, G.R. (1993) Functional characterization of elements in a human U6 small nuclear RNA gene distal control region. Mol Cell Biol, 13, 4670-4678. 31. Murphy, S., Pierani, A., Scheidereit, C., Melli, M. and Roeder, R.G. (1989) Purified octamer binding transcription factors stimulate RNA polymerase III--mediated transcription of the 7SK RNA gene. Cell, 59, 1071-1080. 32. Sturm, R.A., Das, G. and Herr, W. (1988) The ubiquitous octamer-binding protein Oct-1 contains a POU domain with a homeo box subdomain. Genes Dev, 2, 1582-1599. 33. Kleinert, H., Bredow, S. and Benecke, B.J. (1990) Expression of a human 7S K RNA gene in vivo requires a novel pol III upstream element. EMBO J, 9, 711-718. 34. Kunkel, G.R., Cheung, T.C., Miyake, J.H., Urso, O., McNamara-Schroeder, K.J. and Stumph, W.E. (1996) Identification of a SPH element in the distal region of a human U6 small nuclear RNA gene promoter and characterization of the SPH binding factor in HeLa cell extracts. Gene Expr, 6, 59-72. 35. Schaub, M., Myslinski, E., Schuster, C., Krol, A. and Carbon, P. (1997) Staf, a promiscuous activator for enhanced transcription by RNA polymerases II and III. EMBO J, 16, 173-181. 36. Dahlberg, J.E. and Blattner, F.R. (1975) Sequence of the promoter-operator proximal region of the major leftward RNA of bacteriophage lambda. Nucleic Acids Res, 2, 1441-1458. 37. Lerner, M.R., Andrews, N.C., Miller, G. and Steitz, J.A. (1981) Two small RNAs encoded by Epstein-Barr virus and complexed with protein are precipitated by antibodies from patients with systemic lupus erythematosus. Proc Natl Acad Sci U S A, 78, 805-809. 38. Howe, J.G. and Shu, M.D. (1989) Epstein-Barr virus small RNA (EBER) genes: unique transcription units that combine RNA polymerase II and III promoter elements. Cell, 57, 825-834. 39. Geiduschek, E.P. and Tocchini-Valentini, G.P. (1988) Transcription by RNA polymerase III. Annu Rev Biochem, 57, 873-914. 40. Rosa, M.D., Gottlieb, E., Lerner, M.R. and Steitz, J.A. (1981) Striking similarities are exhibited by two small Epstein-Barr virus-encoded ribonucleic acids and the adenovirus-associated ribonucleic acids VAI and VAII. Mol Cell Biol, 1, 785-796. 41. Eilebrecht, S., Pellay, F.X., Odenwalder, P., Brysbaert, G., Benecke, B.J. and Benecke, A. (2008) EBER2 RNA-induced transcriptome changes identify cellular processes likely targeted during Epstein Barr Virus infection. BMC Res Notes, 1, 100. 42. Graham, F.L. and van der Eb, A.J. (1973) Transformation of rat cells by DNA of human adenovirus 5. Virology, 54, 536-539. 43. Dignam, J.D., Martin, P.L., Shastry, B.S. and Roeder, R.G. (1983) Eukaryotic gene transcription with purified components. Methods Enzymol, 101, 582-598. 44. Chomczynski, P. and Sacchi, N. (1987) Single-step method of RNA isolation by acid guanidinium thiocyanate-phenol-chloroform extraction. Anal Biochem, 162, 156-159. 45. Zuker, M. (1989) Computer prediction of RNA structure. Methods Enzymol, 180, 262-288. 46. Noth, S. and Benecke, A. (2005) Avoiding inconsistencies over time and tracking difficulties in Applied Biosystems AB1700/Panther probe-to-gene annotations. BMC Bioinformatics, 6, 307. 47. Noth, S., Brysbaert, G. and Benecke, A. (2006) Normalization using weighted negative second order exponential error functions (NeONORM) provides robustness against asymmetries in comparative transcriptome profiles and avoids false calls. Genomics Proteomics Bioinformatics, 4, 90-109. 48. Noth, S., Brysbaert, G., Pellay, F.X. and Benecke, A. (2006) High-sensitivity transcriptome data structure and implications for analysis and biologic interpretation. Genomics Proteomics Bioinformatics, 4, 212-229. 49. Wilhelm, E., Kornete, M., Targat, B., Vigneault-Edwards, J., Frontini, M., Tora, L., Benecke, A. and Bell, B. TAF6delta orchestrates an apoptotic transcriptome profile and interacts functionally with p53. BMC Mol Biol, 11, 10. 50. Surig, D., Bredow, S. and Benecke, B.J. (1993) The seemingly identical 7SK and U6 core promoters depend on different transcription factor complexes. Gene Expr, 3, 175-185. 51. Shannon P, Markiel A, Ozier O, Baliga NS, Wang JT, Ramage D, Amin N, Schwikowski B, Ideker T. (2003) Cytoscape: a software environment for integrated models of biomolecular interaction networks. Genome Research 13(11):2498-504. 52. Haaland, R.E., Herrmann, C.H. and Rice, A.P. (2005) siRNA depletion of 7SK snRNA induces apoptosis but does not affect expression of the HIV-1 LTR or P-TEFb-dependent cellular genes. J Cell Physiol, 205, 463-470.
References
Pubmed : http://www.ncbi.nlm.nih.gov/pubmed/21282977
RNA Biol. 2011 Jan 1;8(1). [Epub ahead of print] HMGA1-dependent and independent 7SK RNA gene regulatory activity. Eilebrecht S, Bécavin C, Léger H, Benecke BJ, Benecke A. Institut des Hautes Études Scientifiques & CNRS USR3078; Bures sur Yvette, France.