DNA-bound transcription factors

In this section we describe two signaling pathways in which the extracellular signal results in regulated gene expression through a phosphorylation cascade. The first example involves cAMP and its activation of a kinase, which translocates to the nucleus and phosphorylates a DNA-bound transcription factor. The second illustrates how phosphorylation of a cytosolic protein by a membrane-bound kinase modulates nuclear localization, and subunit... 

TBP binds to the TATA box in the minor groove of DNA (most transcription factors bind in the major groove) and causes an approximately 100-degree bend or kink of the DNA helix. This bending is thought to facilitate the interaction of TBP-associated factors with other components of the transcription initiation complex and possibly with factors bound to upstream elements. Although defined as a component of class II gene promoters, TBP, by virtue of its association with... 

Figure 43-11. The hormone response transcription unit. The hormone response transcription unit is an assembly of DNA elements and bound proteins that interact, through protein-protein interactions, with a number of coactivator or corepressor molecules. An essential component is the hormone response element which binds the ligand (A)-bound receptor (R). Also Important are the accessory factor elements (AFEs) with bound transcription factors. More than two dozen of these accessory factors (AFs), which are often members of the nuclear receptor superfamily, have been linked to hormone effects on transcription. The AFs can interact with each other, with the liganded nuclear receptors, or with coregulators. These components communicate with the basal transcription complex through a coregulator complex that can consist of one or more members of the pi 60, corepressor, mediator-related, or CBP/p300 families (see Table 43-6).

How do the distantly bound transcription factors contact the basic transcriptional machinery and instruct Pol II when to start transcription Although there are linkers to establish these contacts, the chromatin complex itself helps to make the contacts. DNA is highly condensed, suprahelical, and often bends on binding a dimeric transcription factor, bringing the transcriptional regulators closer together (Fig. 9.4). 

HMGI binds to the minor groove of DNA regardless of the sequence and, as a result, bends the DNA molecule sharply. This bending of the enhancer DNA permits bound transcription factors to interact properly. The Inherently... 

R235 T. Shrivastava and T. H. Tahirov, Tree-Dimensional Structures of DNA-Bound Transcriptional Regulators , in Methods in Molecular Biology (New York, NY, United States), ed. I. Ladunga, Springer, 2010, Vol. 674, Computational Biology of Transcription Factor Binding, p. 43. 

The main variation of EM that has been reported is cryo-electron microscopy (GEM). Of the reports on the use of GEM during this review period the most-studied structure is the ribosome (from various organisms) and its associated machinery. There have also been a number of studies on various viruses. Other studies that have been reported include ribonucleoproteins, the RNA guide surveillance complex from E.coli, a p53 tetramer bound to a DNA-encoding transcription factor response element, human RXR/VDR nuclear receptor in complex with its DR3 target DNA, a complex (UPF-EJG) from eukaryotic nonsense-mediated mRNA decay,and of a DNA origami structure. ... 

The general transcription factor TFllD is believed to be the key link between specific transcription factors and the general preinitiation complex. However, the purification and molecular characterization of TFllD from higher eucaryotes have been hampered by its instability and heterogeneity. All preparations of TFllD contain the TATA box-binding protein in combination with a variety of different proteins called TBP-associated factors, TAFs. When the preinitiation complex has been assembled, strand separation of the DNA duplex occurs at the transcription start site, and RNA polymerase II is released from the promoter to initiate transcription. However, TFIID can remain bound to the core promoter and support rapid reinitiation of transcription by recruiting another molecule of RNA polymerase. 

Figure 9.12 Schematic diagram of the structure of the heterodimeric yeast transcription factor Mat a2-Mat al bound to DNA. Both Mat o2 and Mat al are homeodomains containing the helix-turn-helix motif. The first helix in this motif is colored blue and the second, the recognition helix, is red. (a) The assumed structure of the Mat al homeodomain in the absence of DNA, based on Its sequence similarity to other homeodomains of known structure, (b) The structure of the Mat o2 homeodomain. The C-terminal tail (dotted) is flexible in the monomer and has no defined structure, (c) The structure of the Mat a 1-Mat a2-DNA complex. The C-terminal domain of Mat a2 (yellow) folds into an a helix (4) in the complex and interacts with the first two helices of Mat a2, to form a heterodimer that binds to DNA. (Adapted from B.J. Andrews and M.S. Donoviel, Science 270 251-253, 1995.)...

DNA binding by TBP is strongly dependent on the presence of T-A base pairs in the TATA box. Bending allows remote sites on the DNA, with their bound cognate specific transcription factors, to come close together such that the proteins can interact to form the transcriptional preinitiation complex. 

Glover, J.N.M., Harrison, S.C. Crystal structure of the het-erodimeric bZIP transcription factor c-Fos-c-Jun bound to DNA. Nature 373 257-261, 1995. 

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