| ALTERNATIVE APPROACHES TO GENE REGULATION IN HUMANS
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| Figure 33.5 A 'standard' zinc finger and a steroid receptor zinc finger. Zinc fingers are commonly occurring sequences that allow protein binding to double-stranded DNA. X, any intervening amino acid. |
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Figure 33.6 Similarity between different steroid receptors. The DNA-binding and hormone-binding regions of steroid receptors share a high degree of homology. The estrogen receptor is less similar to the glucocorticoid receptor than are the others. AR, androgen receptor; ER, estrogen receptor; GR, glucocorticoid receptor; MR, mineralocorticoid receptor; PR, progesterone receptor; nnn, anonymous nucleotides. Numbers denote % homology to sequence in GR. |
| DNA in the cell nucleus is packaged into nucleosomes and higher order structures in association with histones and other proteins (Chapter 30). Thus, the promoters of some genes may not be readily accessible to transcription factors, even if the transcription factors themselves are present in the nucleus. It has become evident that the degree of packaging
of a promoter and the presence, absence or precise location of nucleosomes on a promoter can have major effects on the degree of access for both sequence-specific transcription factors and the RNAPol II complex associated with general transcription factors. Condensed chromatin is usually not a good template for transcription and in many cases it is necessary for chromatin remodeling to occur before transcription proceeds. Histone packaging, nucleosome stability and, therefore, the accessibility of DNA is controlled by reversible acetylation and deacetylation of lysine residues in the amino terminal regions of the core histones, particularly histones H3 and H4. Histone acetyl transferases (HAT) transfer acetyl groups from acetyl-CoA to the amino group of lysines, neutralizing the charge on the lysine residue and the strength of histone-DNA interactions, thereby permitting the relaxation of the nucleosome. Conversely, enzymes that remove the acetyl groups and promote the local condensation of chromosomes are known as histone deacetylases.
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| Reversible acetylation and deacetylation of histones is important in controlling the activation of promoters. Indeed, some transcription factors or transcription co-activators have HAT activity themselves and can remodel chromatin. In the case of some promoters, binding of a transcription factor may result in repositioning of the nucleosomes the next time the DNA replicates, and then other transcription factors can bind and so the gene becomes more expressed after cell division. The dynamic interplay of chromatin structure, transcription factor and cofactor binding is important in determining whether a gene is transcribed and how efficiently the RNA polymerase copies it.
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