Dear all,
Recently, i am working on transcription factor binding sites on the specific promoter. As you know sometimes there is one binding site for different transcription factors ( For example: ATF transcription factor), in this condition which one comes first in a same situation? or a complicated of transcription factors complex provide a cascade of signaling?
Please explain in both conditions (If there is both) which method is the best one to understand this network?
Im not sure if I understand your question entirely. However, I recently read a publication about two transcription factors competing for approximately the same binding site. The sequential binding of factor 1 followed by factor 2 in this case determines differentiation towards a cardiomyocyte phenotype. Hopefully this helps.
Article Sequential Binding of MEIS1 and NKX2-5 on the Popdc2 Gene: A...
Hi Shahrooz,
hard to answer your request since it can be really specific, from gene to gene. In general, promotors are containing lot of regulation sequences for some TF that can be targeted by other TF and enzymes.
take a lot at this picture, will not help but will tell you it's not simple (https://upload.wikimedia.org/wikipedia/commons/8/80/Transcription_Factors.svg).
fred
Dear Shahrooz,
The theory:
Interaction of a transcription factor (TF) with DNA it is dynamic, and depending of the specific case interpretation it is different. First, usually different TFs do not bind to the exactly same binding site (BS) unless they form a complex, in this case you can cansider the complex as a "unique TF", in other case they can be so close that fisically both TF can't be bound at the same time.
If TFs work independently they can act (1) cooperatively or (2) in competition. In (1) you can have 2 possibilities: (1a) One of the TF needs the other TF bealready bound, then it has sense to talk about a sequence where one of the TF bind first; (1b) both TF can bind the BS, but if one of the TF is already bound (doesn't matter which one) the binding of the second TF it is easier. In (2) the binding affinity of each TF and their concentration will determine the binding equilibrium, so which one if effectively bound.
Method:
In any case, a good aproximation is being able to do in vitro binding (by EMSA for instance, and also by QuMFRA; you can see these methods and references in our paper (Article Prediction of Regulatory Interactions from Genome Sequences ...
) and evaluate the relative affinity, and what happens when each TF of both are present. It can give you clues about the TF binding and TFs interaction. Of course you can also use ChIP-Seq, more expensive, to compare samples with the presence or absence of the TFs and interpret those results.- Badges
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