Regulating genes

Disease States. Rickets is the most common disease associated with vitamin D deficiency. Many other disease states have been shown to be related to vitamin D. These can iavolve a lack of the vitamin, deficient synthesis of the metaboUtes from the vitamin, deficient control mechanisms, or defective organ receptors. The control of calcium and phosphoms is essential ia the maintenance of normal cellular biochemistry, eg, muscle contraction, nerve conduction, and enzyme function. The vitamin D metaboUtes also have a function ia cell proliferation. They iateract with other factors and receptors to regulate gene transcription. 

Rosenfeld, M.G. POU-domain transcription factors pou-er-ful developmental regulators. Genes Dev. 5 897-907, 1991. 

Allergy. Figure 5 Glucocorticoids regulate gene expression, resulting in a decrease of cytokine and mediator release. 

In higher eukaiyotes, most of the chromosomal DNA carries 5-methyl-cytidine residues located in CpG sequence motives. There is a close correlation between transcriptional inactivation and methylation. On the other hand, considerable evidence shows that regions of DNA that are actively engaged in transcription lack 5-methyl-cytidine nucleotides in CpG motivs. Hence DNA methylation is a means how cells regulate gene expression. DNA methylation which is catalyzed by DNA methyltransferases is the best characterized epigenetic mechanism. 

STAT binding site in the promoter region of cytokine-responsive genes. It is nonameric palindrome with relaxed sequence specificity.) sites, to regulate gene expression. Tyrosine phosphatases located in the nucleus then dephosphorylate STAT molecules (Fig. 1). 

Peroxisome Proliferator-Activated Receptors. Figure 3 Transcription of PPAR target genes. A schematic representation of the transcription of PPAR-regulated genes in the absence (a) and presence (b) of PPAR ligand. Abbreviations PPAR-RE, peroxisome proliferator-activated receptor-response element RNA Pol II, RNA polymerase II TATA-BP, TATA-binding protein. 

As more is learned about the chromosomal effects on HS gene expression, it is important to point out that these genes are actually a subset of inducible responses to cellular stress. Not all of these inducible responses involve HSF, and this indicates that cells have diversified transcriptional responses to cope with different types of stress. This diversification is manifested by glucose regulated genes (grp), as well as the metallothionein and oxidant-injury genes (Watswich, 1988 Storz et al., 1990 Devary et al., 1992 Skroch et al., 1993 Xu, 1993). 

As illustrated in Table 43-5, the discovery of the nuclear receptor superfamily has led to an important understanding of how a variety of metabolites and xenobi-otics regulate gene expression and thus the metabolism, detoxification, and elimination of normal body products and exogenous agents such as pharmaceuticals. Not surprisingly, this area is a fertile field for investigation of new therapeutic interventions. 

Vitamin D is not strictly a vitamin since it can be synthesized in the skin, and under most conditions that is its major source. Only when sunlight is inadequate is a dietary source required. The main function of vitamin D is in the regulation of calcium absorption and homeostasis most of its actions are mediated by way of nuclear receptors that regulate gene expression. Deficiency—leading to rickets in children and osteomalacia in adults—continues to be a problem in northern latitudes, where sunlight exposure is poor. 

Mahajan SD, Schwartz SA, Shanahan TC, Chawda RP, Nair MP (2002) Morphine regulates gene expression of alpha- and beta-chemokines and their receptors on astroglial cells via the opioid mu receptor. J Immunol 169 3589-3599... 

Sandur, S.K. et ah, Plumbagin (5-hydroxy-2-methyl-1,4-naphthoquinone) suppresses NF-kappa B activation and NF-kappa B-regulated gene products through modulation of p65 and I-kappa-B-alpha kinase activation, leading to potentiation of apoptosis induced by cytokine and chemotherapeutic agent, J. Biol. Chem., 281, 17023, 2006. 

NF-KB-regulated gene products and TAKl-mediated NF-kB activation. Blood2007,109, 2727-2735. 

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