Specificity in the regulation of eukaryotic gene transcription.

The regulation of eukaryotic gene transcription poses major challenges in terms of the innumerable protein factors required to ensure tissue or cell-type specificity. While this specificity is sought to be explained by the interaction of cis-acting DNA elements and the trans-acting protein factor(s), considerable amount of degeneracy has been observed in this interaction. Immunoglobulin heavy chain gene expression in Β cells and liver-specific gene expression are discussed as examples of this complexity in this article. Heterodimerization and post-translational modification of transcription factors and the organization of composite promoter elements are strategies by which diverse sets of genes can be regulated in a specific manner using a finite number of protein factors.

Developmental regulation of cytochrome P-450 (b+e) and glutathione transferase (Ya+Yc) gene expression in rat liver.

The expression of cytochrome P-450 (b+e) and glutathione transferase (Ya+Yc) genes has been studied as a function of development in rat liver. The levels of cytochrome P-450 (b+e) mRNAs and their transcription rates are too low for detection in the 19-day old fetal liver before or after phenobarbitone treatment. However, glutathione transferase (Ya+Yc) mRNAs can be detected in the fetal liver as well as their induction after phenobarbitone treatment can be demonstrated. These mRNAs contents as well as their inducibility with phenobarbitone are lower in maternal liver than that of adult nonpregnant female rat liver. Steroid hormone administration to immature rats blocks substantially the phenobarbitone mediated induction of the two mRNA families as well as their transcription. It is suggested that steroid hormones constitute one of the factors responsible for the repression of the cytochrome P-450 (b+e) and glutathione transferase (Ya+Yc) genes in fetal liver.

Factors regulating the transcription of eukaryotic protein coding genes and their mechanism of action—A review.

Protein factors play a crucial role in establishing gene-specific and cell-specific regulation of the process of transcription. These include general transcription factors which recognize TATA and CCAAT boxes and which form components of the RNA polymerase II system. Specific transcription factors interact with characteristic promoter elements of individual genes. Some of the examples are SP1, glucocorticoid receptor, GCN4, GAL4 and many others. Transcription factors have a DNA binding domain demarcated from the transcription activation domain. Some factors may have an additional ligand (small molecule) binding domain. Typical structural features such as helix-turn-helix motif, zinc finger and leucine zipper have been recognized in the DNA binding domain of the transcription factors. The acidic domain of the protein factors is involved in the transcription activation process. It appears that activation is the result of the combined action of several regulatory proteins binding at different regions of the promoter. Interaction between proteins bound to DNA but seperated by long stretches of nucleotides is facilitated by DNA bending. Functional specificity as well as diversity are feasible with a limited number of transcription factors through alterations in the architecture of interaction between a group of proteins bound to promoter elements.