Genes hormone response elements

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.

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. 1.7. 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...

B. Binding of ligand activates the receptor so that it can bind specific DNA sequences in regulatory regions of target genes that have hormone-response elements (HREs) (Figure 14—5). 

Fig. 3.6. Principles of signal transduction by transmembrane receptors and nuclear receptors, a) transmembrane receptors receive the signal on the cell surface and convert it into an intracellular signal that can be passed on until it reaches the nucleus, b) In signal transduction via nuclear receptors the hormone enters the cell and binds the receptor either in the cytosol (R) or nucleus (R ). Nuclear receptors act as nuclear transcription factors that bind specific DNA elements (HRE hormone responsive element) found in the promotor region of regulated genes to control their transcription rate.

Model of the interaction of T3 with the T3 receptor. A Inactive phase —the unliganded T3 receptor dimer bound to the thyroid hormone response element (TRE) along with corepressors acts as a suppressor of gene transcription. B Active phase — T3 and T4... 

Hormone binding changes the conformation of Rec it forms homo-or heterodimers with other hormone-receptor complexes and binds to specific regulatory regions called hormone response elements (HREs) in the DNA adjacent to specific genes. 

The hormone-receptor complex binds specific regions of DNA, the hormone response elements, and regulates the expression of nearby genes by interacting with transcription factors. 

Regulation of the LDL receptor gene involves a hormone-response element (HRE, see p. 238).] Third, if the cholesterol is not required immediately for some structural or synthetic purpose, it is esterified by acyl CoA cholesterol acyltransferase (ACAT, AC AT transfers a fatty acid from a fatty acyl CoA derivative to cholesterol, producing a cholesteryl ester that can be stored in the cell (Figure 18.21). The activity of ACAT is enhanced in the presence of increased intracellular cholesterol. 

Each steroid hormone diffuses across the plasma membrane of its target cell and binds to a specific cytosolic or nuclear receptor. These receptor-ligand complexes accumulate in the nucleus, dimerize, and bind to specific regulatory DIMA sequences (hormone-response elements) in association with coactivator proteins, thereby causing promoter activation and increased transcription of targeted genes. 

This inability of fully functional receptor complexes to activate a given gene also occurs in normal cells. In new-born chicks, a single injection of oestradiol has a delayed effect on vitellogenin synthesis in liver. Having been exposed once to the hormone, second injections elicit an immediate response. It has been suggested that the first injection demethylates methyl cytosine residues within the hormone response element, thereby allowing receptor attachment [29]. 

Fig. 1. A model for the mechanism whereby steroid hormones regulate rates of gene transcription. Steroids (S) bind with receptors (R) to form a steroid-receptor complex that interacts with DNA sequences called hormone response elements (HRE). These HREs are at variable distances from the gene promoter which frequently consists of upstream promoter elements (UPE) and conserved elements such as TATA box (TATA).

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