The Control of Gene Expression by means of Connectrons

Richard J. Feldmann
Global Determinants, Inc.
Derwood, Maryland, USA

The existence of transcripts from both Gene-Coding and Non-Coding DNA regions produced by the Genome Exploration Research Group at the Institute of Physical and Chemical Research (RIKEN) in Yokohama, Japan makes it possible to determine the complete Connectrome of the Transcriptome of the mouse Genome. The Connectrome is the collection of all the identified Connectrons. A Connectron is a 4-sequence construct composed of two 24-base or longer control sequences (called C1 and C2) that are produced as RNA by the transcription of either Gene-Coding or Non-Coding DNA. The other two target sequences (called T1 and T2) are short regions of double-stranded DNA. The first RNA sequence (C1) binds to the left DNA sequence (T1) to form a triple-stranded (RNA/DNA/DNA) Hoogsteen helix. The second RNA sequence (C2) which is a continuation of the C1 sequence binds to the second target DNA sequence (T2) which can be anywhere from 0.5kb to 3mb from the T1 sequence. The effect of the creation of a Connectron is to form a loop of DNA which then can condense into tightly coiled 30nm chromatin structure. Gene-Coding or Non-Coding DNA in this chromatin-condensed loop is not available for transcription for the lifetime of the Connectron construct. The lifetime of a Connectron is thought to be proportional to the length of the shorter of the C1/T1 and C2/T2 triple-stranded Hoogsteen helices.

About 40% of the mouse Genome is transcribed. We have analyzed the Connectrome of the RIKEN mouse Transcriptome and found that although the Non-Coding DNAs are only 1/3 of the total transcripts, they produce about 1/2 of the Connectrons. We hypothesize that Non-Coding transcripts control their own expression and that of Gene-Coding DNA. Similarly, Gene-Coding transcripts control their own expression and that of Non-Coding DNA. There seems to be complete symmetry of expression and expression control. The difference between a piece of Gene-Coding DNA and a piece of Non-Coding DNA is that for the former a protein is eventually produced whereas the latter produces only pure expression control. This shows for the first time that Non-Coding DNA plays an important role in cellular expression control and that the idea of ?junk DNA? can safely be discarded.

Recent calculations indicate that viruses interact with the host genomes by means of Connectrons. The question of how a virus takes over the reproductive machinery of a cell, produces many copies of its genome and then triggers cell death may be capable of being answered.

This talk will describe the basic properties of Connectrons as logical expression-control agents. In addition, many other properties of the Connectrome will be discussed. Connectron computations have been done on almost all of the several hundred genomes available on the server at the National Center for Biotechnology Information (NCBI) of the NIH. The properties common to these many genomes will be discussed.

The biomedical, agronomic and economic implications of Connectrons will be discussed.

I have approached the problem of the control of gene expression from a purely informatic viewpoint. I am just now forming a collaboration with Dr. Javed Siddiqi at DNA Technologies, Inc. in Gaithersburg, Maryland to demonstrate in E. coli, mouse and human that Connectrons exist and have utility.

The previous Connectron workshops have been fun. Connectrons are still far-out but their time is coming. Each workshop attracts people who are willing to leave their rut and think about something different for a couple of hours.

Speaker:

Richard J. Feldmann, Global Determinants, Inc. (rjfeldma@globaldeterminants.com)
"Connectron Structure of Small Bacterial and Archeal Genomes"

This page last updated Friday, 15-Dec-2006 10:20:23 EST