I understand that eukaryotic DNA needs to have its chromatin \"opened\" by chrom
ID: 22824 • Letter: I
Question
I understand that eukaryotic DNA needs to have its chromatin "opened" by chromatin remodeling complexes in order for the transcription initiation factors to form, but my biochemistry book mentions "activators" as being able to bind to the promoter sites even when chromatin is condensed and then it can recruit these remodeling complexes...then my lecture notes mention "pioneering transcription factors" and I can't seem to find a clear definition of what these are. Are "activators" considered pioneering transcription factors?Explanation / Answer
Even though the activators bind promoter sites even in condensed chromatin, they are binding in an inactive form or may not be binding at all. The pioneering transcription factors depend on the mechanism of gene regulation. Very commonly the target cell is stimulated by a hormone or by a regulating cell (example a surface molecule on the membrane of a T cell). In either case there is a signal transduction acting on the cell membrane that elicits the activation of a "second messsenger" like cyclic AMP, with or without a phosphorylation of some protein by local enzymes called kinases (or the dephosphorylation of some protein by local enzymes called phosphorylases). Kinases and phosphorylases become active under successful signal transduction, and the newly transformed protein that they have just acted upon starts a chain of event that leads to some molecules moving into the nucleus and activating the activator already bound to the promoter, or recruiting it for binding. In some mechanisms of gene regulation, the hormone that initiates the signal transduction does not stop at the cell membrane. Some hormones penetrate into the cytoplasm and there activate their own second messenger. Other hormones that need to mediate quick instant responses, penetrate into the nucleus and modify the activators themselves. Whatever the mechanism by which this signal transduction starts the process of upregulating the transcription of the target gene, the modified messengers (not always proteins, sometimes they are ions, steroids, peptides) interact with cytoplasmic and of course nuclear components. The result of that interaction is the recruitment of the correct RNA polymerase with the correct assemblage of subunits and transcription factors, and the localized loosening of the chromatin structure in the right places. These first molecules that mediate the process are collectively known as pioneering transcriptor factors, a general term for different processes. (Some genes are even upregulated at places other than the transcription site, for example splicing, editing, but even regulation at the transcription level exhibits a lot of variability.) At some point, everything is ready for transcription. At that moment the pioneering mechanisms have accomplished their goal, and the transcription site exhibits the effective transcription factors, and when needed, the soon-to-be-needed termination factors, if any.