"Models of successive levels of resolution during individul gene transcription".
John H. Frenster 1, and Jeannette A. Hovsepian 2,
Divisions of 1 Medical Oncology, and of 2
Diagnostic
Imaging,
Stanford University School of Medicine, Stanford, California 94305,
USA
Phone: 650/367-6483, e-mail: frensterjh@aol.com
, hovsepianj@aol.com , http://www.euchromatin.net/
Supported in part by a USPHS Research Career Development Award (CA-17857)
from the National Cancer Institute.
Network simulation studies require integration of gene activity at several levels.
Recent and on-going studies have revealed three levels of resolution showing pervasive interleaved transcription (Gingeras TR, "Mapping the strand-specific transcriptome of fission yeast", Nature Genetics 40: 935 (August, 2008). These studies have included the levels of multiple gene clusters, of overlapping primary transcripts, and of individual gene loci (ibid.).
Newer studies have suggested a deeper level of resolution distinguishing transcription on one DNA strand from that on the opposing DNA strand within a single gene locus (Dutrow N, et al., "Dynamic transcriptome of S. pombe shown by RNA-DNA hybrid mapping", Nature Genetics 40: 977 (August, 2008). The products of such transcription include both coding and non-coding RNAs, sense and antisense orientations, and single and paired duplexes.
Among the latter, the increasing importance of RNA-DNA and RNA-RNA duplexes during regulation of gene transcription is being recognized as crucial to gene selectivity and gene specificity. The recent studies of RNA-RNA interactions within promoter sites and enhancer sites of the same gene product exemplifies such research (Schwartz JC, et al., "Antisense transcripts are targets for activating small RNAs", Nature Structural & Molecular Biology, 15: 842 (August, 2008), as does the study of individual genes on one chromosome and throughout the euchromatin of one cell (Mikkelsen TJ, et al., "Dissecting direct reprogramming through integrative genomic analysis", Nature 454: 49 (July 3. 2008).
A preliminary network simulation of these data for several linked genes reveals driving forces from initiation levels which determine kinetics thoughout the particular gene network.
These diverse data re-assert the need and importance of high-resolution
isolation techniques and comprehensive composite structures in analyzing
network interactions within intact living cells.
Level of Resolution
Transcription System
Biological Effects
1. DNase I probes Active gene clusters Location, size, number
2. FISH RNA probes Single gene locus Location, dynamics
3. 10 nm micro-fibril Isolated euchromatin Native state loci
4. 20 nm paired fibrils Isolated euchromatin Interacting loci
5. DNA-DNA tetraplex Kissing chromosomes Interacting DNAs
6. RNA enhancer Transcript selection Phenotype
7. RNA promoter Transcript initiation Plasticity
8. DNA anticoding strand Activator receptor Ultimate receptor
9. DNA coding strand RNA Pol II receptor First template
10. DNA-RNA hybrid Transcript product First product
11. RNA Pol II velocity Ripple activations Group effect
12. RNA RefSeq assays Whole genome Single gene
13. RNA 5’ ends Transcript product Single transcript
14. RNA Re-programming Transcript product Therapeutic agent
15. Embryonic RNA Whole genome Ultimate oncogene
16. EMT, MET RNA Whole genome Metastatic oncogene
17. RNA selection window Whole cell Molecular evolution
18. RNA selection linkage Multi-gene networks Cellular evolution
www.euchromatin.net/Frenster30.htm
1. Frenster JH, and Hovsepian JA, "Models of Embryonic RNA Initiating and Reverting Adult Neoplasms". Section 6 (Cancer Genetics) of the XX International Congress of Genetics, "Understanding Living Systems", Berlin, Germany, July 12-17, 2008.
2. Schwartz JC, Younger ST, Nguyen N-B, Hardy DB, Monia BP, Corey
DR, and Janowski BA,
"Antisense transcripts
are targets for activating small RNAs".
3. Frenster JH, and Hovsepian JA, “Models of Embryonic Gene-Induced Initiation and Reversion of Adult Neoplasms”.
4. Ogawa Y, Sun BK, and Lee JT,
"Intersection of
the RNA Interference and X-Inactivation Pathways".
5. Place RF, Li L-C, Pookot D, Noonan EJ, and Dahiya R, "MicroRNA-373 induces expression of genes with complementary promoter sequences".
6. Borel C, Gagnebin M, Gehrig C, Kriventseva EV, Zdobnov EM, and
Antonarakis SE,
"Mapping
of Small RNAs in the Human ENCODE Regions".
7. Zhu X, Ling J, Zhang L, Pi W, Wu M, and Tuan D, "A facilitated tracking and transcription mechanism of long-range enhancer function".
8. Frenster JH, and Hovsepian JA, "DNase-I Ultrastructural Probe Sites and Kissing Chromosomes".
9. Han J, Kim D, and Morris KV, "Promoter-associated RNA is required for RNA-directed transcriptional gene silencing in human cells".
10. Murray JI, Bao Z, Boyle TJ, Boeck ME, Mericle BL, Nicholas TJ,
Zhao Z, Sandel MJ, and Waterston RH,
"Automated analysis of embryonic gene expression with cellular resolution
in C. elegans",
Nature Methods - vol. 5; no. 8, pp. 703 - 709 (August, 2008)
http://www.nature.com/nmeth/journal/v5/n8/abs/nmeth.1228.html.
11. Meisner LF, and Frenster JH,
"In Vivo
Evolution within Radiation-Induced Clones of Human Lymphocytes".
12. Prabhakar S, Visel A, Akiyama JA, Shoukry M, Lewis KD,
Holt A, Plajzer-Frick I, Morrison H, FitzPatrick DR, Afzal V, Pennacchio
LA, Rubin EM, and Noonan JP,
"Human-Specific
Gain of Function in a Developmental Enhancer".
Links to
Euchromatin Activator RNA Reviews:
Links to
Euchromatin Activator RNA Research:
Links to Ultrastructural
Probes of DNase I-Sensitive Sites:
Links to
RNA as a Therapeutic Agent:
Links to Hodgkin Lymphoma
Immuno-Pathology:
Links to Activated
T-Lymphocyte Immunotherapy:
Links to Medical
Systems Biology:
Links to Selective
Gene Transcription:
Links to RNA-Induced
Epigenetics:
Links to RNA-Induced
Embryogenesis:
Links to RNA and
Biological Causality:
Links to Reprogramming
and Neoplasia:
A Brief History of Activator RNA:
"Ultrastructural Probes of Active DNA Sites, and the RNA Activators of DNA". (PowerPoint Presentation).