3 research outputs found
How the DNA sequence affects the Hill curve of transcriptional response
The Hill coefficient is often used as a direct measure of the cooperativity
of binding processes. It is an essential tool for probing properties of
reactions in many biochemical systems. Here we analyze existing experimental
data and demonstrate that the Hill coefficient characterizing the binding of
transcription factors to their cognate sites can in fact be larger than one --
the standard indication of cooperativity -- even in the absence of any standard
cooperative binding mechanism. By studying the problem analytically, we
demonstrate that this effect occurs due to the disordered binding energy of the
transcription factor to the DNA molecule and the steric interactions between
the different copies of the transcription factor. We show that the enhanced
Hill coefficient implies a significant reduction in the number of copies of the
transcription factors which is needed to occupy a cognate site and, in many
cases, can explain existing estimates for numbers of the transcription factors
in cells. The mechanism is general and should be applicable to other biological
recognition processes.Comment: 9 pages, 7 figure
Classes of fast and specific search mechanisms for proteins on DNA
Problems of search and recognition appear over different scales in biological
systems. In this review we focus on the challenges posed by interactions
between proteins, in particular transcription factors, and DNA and possible
mechanisms which allow for a fast and selective target location. Initially we
argue that DNA-binding proteins can be classified, broadly, into three distinct
classes which we illustrate using experimental data. Each class calls for a
different search process and we discuss the possible application of different
search mechanisms proposed over the years to each class. The main thrust of
this review is a new mechanism which is based on barrier discrimination. We
introduce the model and analyze in detail its consequences. It is shown that
this mechanism applies to all classes of transcription factors and can lead to
a fast and specific search. Moreover, it is shown that the mechanism has
interesting transient features which allow for stability at the target despite
rapid binding and unbinding of the transcription factor from the target.Comment: 65 pages, 23 figure