Quiz 15: Gene Regulation in Eukaryotes I: Transcriptional and Translation Regulation

Biology

There are four common points that control in eukaryotic gene regulation. • DNA chromatic structure • Transcription • RNA level • Protein level DNA chromatic structure includes gene amplification, the arrangement and composition of nucleosomes influence the transcription. DNA methylation inhibits transcription. Transcription: The regulatory transcription factors activate or inhibit transcription. RNA level: It includes RNA procession and regulation of splicing through SR proteins. Protein level: It involves feedback inhibition and covalent modification regulates protein function.

DNA (Deoxyribo Nucleic Acid) is present in cells in the form of a compacted structure called Chromatin. DNA complexes with proteins called Histones which condenses extensively to form a 30 nm fibre; the predominant form during interphase when gene expression occurs. The chromatin is a dynamic structure that alternates between highly condensed and highly extended conformations, and this nature is essential to regulate gene expression. In its compact state, chromatin is not accessible to DNase I (Deoxyribo nuclease I). The enzyme can act on DNA in chromatin only in its extended conformation. DNase sensitivity of a region of chromatin serves as an indication for gene activity. The following changes occur in a region of chromatin which is transcriptionally active and is thus sensitive to DNase I: • ATP (Adenosine triphosphate) dependent chromatin remodelling : The net result of this remodelling is a change in the locations of nucleosomes. This change may also involve a shift in the spacing of nucleosomes which loosen the level of chromatin compaction • Demethylation of DNA : There are reduced levels of 5-methylcytosine at CpG dinucleotides (Cytosine-P-P-Guanosine) due to demethylation • Depletion of H1 histone proteins : H1 histone protein stabilizes the 30 nm fibre structure. Removal of H1 helps the chromatin transit to the more open 10 nm fibre • Acetylation of core histones : Lysines at the N-terminal tails of core histones are acetylated. This acetylation neutralizes the positive charges All of these changes makes a gene transit from an inactive state to an active statE.

The methylation of DNA (deoxyribonucleic acid) can regulate gene expression in tissue-specific way, because de novo methylation occurs in particular tissue. The later stages of development would be turned off if genes are methylated in the germ line to prevent their expression. However, gene was methylated in a germ line it would have to be demethylated during gamete formation. Specific genes are methylated during Oogenesis or Spermatogenesis, but not both. Following fertilization, the pattern of methylation is maintained in the offspring. If gene is methylated only during spermatogenesis, the allele that is inherited from the father will be methylated in somatic cells of the offspring, but the maternal allele will remain unmethylateD.