The Transcriptome

The transcriptome can be defined as the complete collection of transcribed elements of the genome. In addition to mRNAs, it also represents non-coding RNAs which are used for structural and regulatory purposes. Alterations in the structure or levels of expression of any one of these RNAs or their proteins can contribute to disease. An understanding of the transcriptome will provide a valuable tool in the research for novel drugs.

Using GeneChip® Technology to Study the Transcriptome

In collaboration with the National Cancer Institute, the transcriptome project seeks to build whole-genome tiling arrays interrogating the genome at resolutions approaching every nucleotide. The possible applications of such arrays include the detection of:

Using GeneChip® technology, researchers involved in the transcriptome project are pushing the limits of transcriptome research by interrogating the genome at resolutions and throughput rates never before attempted. While researchers studying the transcriptome have traditionally focused on the coding part of the genome, early findings from the transcriptome project demonstrate that large regions of the genome beyond the coding segments are transcribed.

This project was initiated with the development of transcription maps for Human chromosomes 21 and 22 at a resolution of 35 base pairs (Kapranov et al, 2002; Kampa et al 2004). The binding sites for the proximal transcription factors Sp1, cMyc and the important tumor suppressor transcription factor p53 have been mapped along these chromosomes ( Cawley et al, 2004). Currently, higher resolution transcription maps (5 base pair resolution) for approximately 30% of the Human Genome (ten chromosomes: 6, 7, 13, 14, 19, 20, 21, 22, X, Y) are being constructed using high density oligonucleotide arrays.

Kapranov, P., Cawley, S. E., Drenkow, J., Bekiranov, S, Strausberg, R. L., Fodor, S.P.A. and Gingeras, T.R., (2002) Large-Scale Transcriptional Activity in Chromosomes 21 and 22. Science 296: 916-919 | supplementary data

Kapranov, P., Sementchenko, V.I. and Gingeras, T.R. (2003) Beyond Expression Profiling: Next Generation Uses Of High Density Oligonucleotide Arrays. Briefings in Functional Genomics and Proteomics 2 (1):47-56

Cawley, S., Bekiranov, S., Ng, H.H., Kapranov, P., Sekinger, E.A., Kampa, D., Piccolboni, A., Sementchenko, V.I., Cheng, J., Williams, A.J., Wheeler, R., Wong, B., Drenkow, J., Yamanaka, M., Patel, S., Brubaker, S., Tammana, H., Helt, G., Struhl, K. and Gingeras, T.R. (2004) Unbiased Mapping of Transcription Factor Binding Sites Along Human Chromosomes 21 and 22 Points to Widespread Regulation of Non-Coding RNAs. Cell 116(4):499-511 | supplementary data

Kampa, D., Cheng, J., Kapranov, P., Yamanaka, M., Brubaker, S., Cawley, S. E., Drenkow, J., Piccolboni, A., Bekiranov, S, Helt, G., Tammana, H. and Gingeras, T.R. (2004) Novel RNAs Identified from an In-depth Analysis of the Transcriptome of Human Chromosomes 21 and 22. Genome Research 14(3):331-342

Bernstein, B.E., Kamal, M., Lindblad-Toh, K., Bekiranov, S., Bailey, D.K., Huebert, D.J., McMahon, S., Karlsson, E.K., Kulbokas, III, E.J., Gingeras, T.R., Schreiber, S.L., and Lander, E.S. (2005) Genomic Maps and Comparative Analysis of Histone Modifications in Human and Mouse Cell 120(2):169-181 | supplementary data

Cheng, J., Kapranov, P., Drenkow, J., Dike, S., Brubaker, S., Patel, S., Long, J., Stern, D., Tammana, H., Helt, G., Sementchenko, V., Piccolboni, A., Bekiranov, S., Bailey, D.K., Ganesh, M., Ghosh, S., Bell, I., Gerhard, D.S., Gingeras, T.R. (2005) Transcriptional Maps of 10 Human Chromosomes at 5-Nucleotide Resolution. Science: Volume 307 | supplementary data

Jeon, Y., Bekiranov, S., Karnani, N., Kapranov, P., Ghosh, S., MacAlpine, D., Lee, C., Hwang, D.S., Gingeras, T.R., Dutta, A. (2005) Temporal profile of replication of human chromosomes. PNAS: Volume 102(18):6419-6424