1/9/2024 0 Comments Inetwork control![]() 2 There is also evidence for sequential TF binding, where binding of a so-called “settler” TF requires prior binding of “pioneer” TFs. Experimental evidence suggests that some TF complexes exist in solution in the nucleoplasm, and therefore presumably preform (at least partially) before binding to DNA. In terms of network structure therefore, inputs from an upstream regulator to its downstream target are rarely simple linear connections, but instead entail synergistic or antagonistic cross-talk between 2 or more upstream regulators. Moreover, binding of multiple TFs to a given regulatory element commonly involves synergistic or antagonistic interactions mediated through higher-order complexes. This review will introduce key concepts, provide an integrated view of selected recent studies, and conclude with an outlook on possible future directions for this field.īinding of multiple TFs to individual gene regulatory elements is consistent with the notion of complex networks of interactions, where the locus of each gene participating in the network receives inputs from multiple upstream regulators. Nevertheless, important progress has been made in recent years, and new emerging technologies suggest that the pace of progress is likely to accelerate. However, much remains to be learned about the way in which individual factors are connected within wider regulatory networks, and how the topology of HSC regulatory networks might affect HSC function. More than 50 transcription factors have been shown to affect the functionality of HSCs. Central to the intracellular decision making processes are transcription factor proteins and their interactions within gene regulatory networks. Given the pivotal nature of HSC decision making for both normal and aberrant hematopoiesis, substantial research efforts have been invested over the last few decades into deciphering some of the underlying mechanisms. Cell fate decision making in HSCs, as indeed in other cell types, is driven by the interplay of external stimuli and intracellular regulatory programs. ![]() ![]() Hematopoietic stem cells (HSCs) are characterized by their ability to execute a wide range of cell fate choices, including self-renewal, quiescence, and differentiation into the many different mature blood lineages.
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