Hormone-responsive element

Hormone response elements (for steroids, T3, retinoic acid, peptides, etc) act as—or in conjunction with— enhancers or silencers (Chapter 43). Other processes that enhance or silence gene expression—such as the response to heat shock, heavy metals (Cd and Zn +), and some toxic chemicals (eg, dioxin)—are mediated through specific regulatory elements. Tissue-specific expression of genes (eg, the albumin gene in liver, the hemoglobin gene in reticulocytes) is also mediated by specific DNA sequences. 

Figure 39-11. Location of hormone response elements (HREs) A, B, and C using the reporter gene-transfection approach. A family of reporter genes, constructed as described in Figure 39-10, can be transfected individually into a recipient cell. By analyzing when certain hormone responses are lost in comparison to the 5 deletion, specific hormone-responsive elements can be located.

Table 43-1. The DNA sequences of several hormone response elements (HREs). ...

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).

Several Hormone Response Elements (HREs) Have Been Defined... 

Hormone response elements resemble enhancer elements in that they are not strictly dependent on position and location. They generally are found within a few hundred nucleotides upstream (50 of the transcrip-... 

White, D. M., et al. (1997). Beta-trace gene expression is regulated by a core promoter and a distal thyroid hormone response element. J. Biol. Chem. 272, 14387-93. Yamashima, T., et al. (1997). Prostaglandin D synthase (beta-trace) in human... 

FIGURE 52-2 There are two modes of hormonal action. (A) Activation of cell-surface receptors and coupled second-messenger systems, with a variety of intracellular consequences. (B) Entry of hormone into the target cell, binding to and activation of an intracellular receptor and binding of the receptor-hormone complex to specific DNA sequences to activate or repress gene expression. DAG, diacylglycerol HRE, hormone-response element. 

The identification of the few genes regulated by hormones, among the multitude of the genes that are expressed in each cell, is a first-order problem. What makes the identification possible is the existence of some short specific sequences of DNA, situated in the promoter region of each gene, that are recognized by the dimer of the hormone receptor. These sequences are called hormone response elements (HRE) (Seiler-Tuyns et al. 1986 Tzukerman et al. 1994). 

Fig. 1.6. Binding domain to DNA. ERs contain two structures called zinc fingers, typical of proteins that interact with DNA. One zinc atom forms four links of coordination with four cysteine residues of the protein structure, which occupy nearby positions, thus leaving a loop of some 15 to 22 aminoacids. The zinc fingers of the receptor are capable of interacting with specific sequences of DNA, the hormone response elements, with which they establish hydrogen bridges and form stable structures...

Fig. 1.7. Interaction of receptor with hormone response element. The hormone response elements are located in the promoter region of genes regulated by hormones with nuclear receptors. They are constituted of sequences from 13 to 15 nucleotides. The elements of estrogen response are formed by two semi-elements, which are sequences of 5 nucleotides, and a spacer of 3 unspecific nucleotides (n). The interaction is produced so that the section of the zinc fingers of the receptor lodges in the main furrow of the DNA double helix...

Role of Receptor-Hormone Response Element Complex... 

Second messengers often involved Protein kinases activated Hormone-receptor complex binds hormone response elements (HRE, of enhancer regions) inDNA... 

HRE - hormone response element TAFs - TBP-associated factors TBP - TATA box-binding protein A-H - basal transcription factors... 

In the nucleus, the hormone-receptor complex binds to nucleotide sequences known as hormone response elements (HREs). These are short palindromic DNA segments that usually promote transcription as enhancer elements (see p. 244). The illustration shows the HRE for glucocorticoids (GRE ... 

The first crystal structure of the LED of the AR in complex with metri-bolone (R1881) was solved by Matias and colleagues in 2000 [38]. The LED has a similar three-dimensional structure to the other agonist-bound steroid receptors, namely the ERa, ERj6 and the PR [38]. The fact that all steroid hormone receptors bind similar hormone response elements (HREs) stands in sharp contrast to the specific activities elicited by application of the steroid... 

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