Combinatorial control of gene expression

Abstract

The complexity and diversity of eukaryotic organisms are a feat of nature's engineering. Pulling the strings of such an intricate machinery requires an even more masterful and crafty approach. Only the number and type of responses that they generate exceed the staggering proportions of environmental signals perceived and processed by eukaryotes. Hence, at first glance, the cell's sparse stockpile of controlling factors does not seem remotely adequate to carry out this response. The question as to how eukaryotes sense and respond to environmental cues has no single answer. It is an amalgamation, an interplay between several processes, pathways, and factors-a combinatorial control. A short description of some of the most important elements that operate this entire conglomerate is given in this paper.

Figure 1

Comparison of the level of induction between the wild type and synthetic enhancers. Multiplication of cis-elements leads to a reduction in specificity and level of induction [8].

Figure 2

Different roles fulfilled by the same transcription factors. Steroid receptors (white shapes) bind to their response elements (REs) after being activated by their ligands (black dots). (a) Binding to different REs recruits a common cofactor and an element-specific cofactor (black octagon and grey shapes, resp.) (b) Binding to adjacent RE recruits a bridging factor. (c) Binding to negative REs recruits corepressors [18].

Figure 3

The figure shows the free-energy landscape of various TF-RE complexes (TF: pale pink; Res: blue, green, and pink/red; cofactor: purple). The binding of the cofactor causes a population shift towards a particular TF-RE complex (indicated by the arrow). As is shown, the TF complex with blue RE is the most stable prior to cofactor binding. After this event, the complex with the red RE is the most stable interaction. By the mechanism stated herein, the binding of the purple co-factor shifts the populations in favour of the TF-red RE complex [31].

Figure 4

Flexible Nature of coactivator Proteins. CBP binds directly to transcription factors and recruit the secondary co-regulators pCAF and SRC-1, all of which have HAT activity. CBP also functions as secondary co-regulators to PGC-1 which directly binds to another transcription factor [23].

Figure 5

lnc-RNA molecules can function via multiple mechanisms as shown here. (I) Lnc-RNAs act as signalling molecules to other molecules that are involved in chromatin remodelling. (II) lnc-RNAs act as decoys and divert the effector molecules away from target DNA. (III) Lnc-RNAs guide the effectors to their respective target sites. (IV) Lnc-RNAs may function as a binding substratum for multiple protein molecules which act on the target gene sequence after assembly [40].