  Cells receive a wide variety of cellular and environmental signals, which
must be processed combinatorially to generate specific and timely genetic
responses. We present here a theoretical study on the combinatorial control and
integration of transcription signals, with the finding that cis-regulatory
systems with specific protein-DNA interaction and glue-like protein-protein
interactions, supplemented by distal activation or repression mechanisms, have
the capability to execute a wide range of control functions encoded in the
regulatory DNA sequences. Using a quantitative model based on the
well-characterized bacterial transcription system, we show explicitly how
various regulatory logic functions can be implemented, by selecting the
strengths and relative positions of the relevant protein-binding DNA sequences
in the cis-regulatory region. The architecture that emerges is naturally
modular and highly evolvable. Our findings suggest that the transcription
regulatory apparatus is a "programmable" computing machine, belonging formally
to the class of Boltzmann machines. We also expose critical shortcomings of the
bacterial transcription systems, which limit the genome-wide adoption of
schemes for complex transcription control, and discuss how they may be overcome
by the eukaryotic transcription systems.
