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On schemes of combinatorial transcription logic.

ABSTRACT: Cells receive a wide variety of cellular and environmental signals, which are often processed combinatorially to generate specific genetic responses. Here we explore theoretically the potentials and limitations of combinatorial signal integration at the level of cis-regulatory transcription control. Our analysis suggests that many complex transcription-control functions of the type encountered in higher eukaryotes are already implementable within the much simpler bacterial transcription system. Using a quantitative model of bacterial transcription and invoking only specific protein-DNA interaction and weak glue-like interaction between regulatory proteins, we show explicit schemes to implement regulatory logic functions of increasing complexity by appropriately selecting the strengths and arranging the relative positions of the relevant protein-binding DNA sequences in the cis-regulatory region. The architectures that emerge are naturally modular and evolvable. Our results suggest that the transcription regulatory apparatus is a "programmable" computing machine, belonging formally to the class of Boltzmann machines. Crucial to our results is the ability to regulate gene expression at a distance. In bacteria, this can be achieved for isolated genes via DNA looping controlled by the dimerization of DNA-bound proteins. However, if adopted extensively in the genome, long-distance interaction can cause unintentional intergenic cross talk, a detrimental side effect difficult to overcome by the known bacterial transcription-regulation systems. This may be a key factor limiting the genome-wide adoption of complex transcription control in bacteria. Implications of our findings for combinatorial transcription control in eukaryotes are discussed.

SUBMITTER: Buchler NE

PROVIDER: S-EPMC404558 | biostudies-literature | 2003 Apr

REPOSITORIES: biostudies-literature

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On schemes of combinatorial transcription logic.

Buchler Nicolas E NE Gerland Ulrich U Hwa Terence T

Proceedings of the National Academy of Sciences of the United States of America 20030417 9

Cells receive a wide variety of cellular and environmental signals, which are often processed combinatorially to generate specific genetic responses. Here we explore theoretically the potentials and limitations of combinatorial signal integration at the level of cis-regulatory transcription control. Our analysis suggests that many complex transcription-control functions of the type encountered in higher eukaryotes are already implementable within the much simpler bacterial transcription system. ...[more]

PMID: 12702751

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Project description:In this work, we describe a logic device in which an act of computation is associated with finding a path connecting input and output ports. The device is based on an active ring circuit comprising electric and magnetic parts. The electric part includes an amplifier, a phase shifter, and an attenuator. The magnetic part is a multi-port magnetic matrix comprising delay lines and frequency filters. Signals propagating on different paths may accumulate different phase shifts. Auto-oscillations occur in the circuit when the magnetic and electric parts match each other to meet the resonance amplitude and phase conditions. The system naturally searches for a resonance path that depends on the position of the electric phase shifter and amplification level. The path is detected by the set of power sensors. The proposed logic device can be used for solving a variety of computational problems. We present the results of numerical modeling illustrating prime factorization and finding the shortest path connected selected points on the mesh. We also present experimental data on the proof-of-the-concept experiment for the two-path device. The magnetic part consists of two waveguides made of single-crystal yttrium iron garnet Y3Fe2(FeO4)3 (YIG) films. Different phase shifts per delay line are achieved by adjusting the magnitude and direction of the bias magnetic field. The auto-oscillation signal changes the propagation path in the magnetic matrix depending on the position of the outer electric phase shifter. The power difference between the active and passive paths exceeds 40 dBm at room temperature. The described logic devices are robust, deterministic, and operate at room temperature. The number of possible paths increases factorial with the size of the mesh. It may be possible to encode information in paths and retrieve it using the external phase shifters and attenuators. Potentially, combinatorial logic devices may compete with quantum computers in functional throughput. Physical limits and constraints are also discussed.

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On schemes of combinatorial transcription logic.

Publications

On schemes of combinatorial transcription logic.

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