Question

List the possible levels of gene expression control in the typical embryo, i.e., from the DNA itself to the final functional protein product. Explain, briefly, how each step could be a control point for gene expression

Answer 1

Regulation of gene expression refers to a very broad term that may occur at various levels which results in the formation of desired protein product. In eukaryotes the regualtion of gene expression exerted at four levels: (i) Transcriptional level: Formation of primary transcript. (ii) Processing level: Regulation of splicing (iii) Transport of mRNA from nucleus to the cytoplasm and (iv) Translational level. Besides these, histones plays major role in gene regulation. In eukaryotes, functionally related genes do not represent an operon but are present on different sites of chromosomes. The structural gene called the split gene is a mosaic of exons and introns. The development and differentiation of embryo into adult organisms are also a result of the coordinated regulation of expression of several sets opf genes.

Histones are gene repressors. They mask the gene activity in non-specific manner. As histones are responsible for the supercoiling of DNA, RNA polymerase molecule would not be able to move along the supercoiled DNA, hence no transcription is possible.

The transfer of genetic information from DNA to mRNA is known as transcription. There are certain gene control regions which includes-(a) promoter- this are sequences present upstream (5' end) of the structural genes. Transcription factors bind to specific nucleotides in promoter region and the binding sites for RNA polymerase lie within this region. (b) Enhancers- Some transcriptional factors, known as activators bind to region called enhancers which increases the rate of transcription. (c) Silencers- some transcription factors known as repressors binds with the region called silencers to suppress the rate of transcription. In eukaryotes the nascent RNA is produced by RNA polymerase II which involves the steps like initiation, elongation and termination. But this nascent RNA or the primary transcript contains both unwanted base sequences (transcribed from introns) alternated with useful base sequences (transcribed from exons). The primary transcript is converted into functional mRNA after post transcriptional processing which involves three steps-(a) Modification of 5' end by capping- Capping at 5' end occurs after the start of transcription catalyzed by guanyl transferase. (b) Tailing- It is the addition of adenylate residues about 200-300 at 3' end in a template-independent manner on newly formed hnRNA with the help of Poly A polymerase. (c) Splicing- It is the process of removal of introns and joining exons in a defined order. Introns are removed by SnRNA and protein complex called SnRNPs.

The translational level involves the polymerisation of amino acids to form a polypeptide in which mRNA defines the order and sequence of amino acids. It involves the following steps- (a) Initiation-The smaller subunit of ribosomes bind with mRNA and moves in 3' direction until it meets a start codon (AUG). It then form complex with larger subunit of ribosome and an initiation tRNA molecule. (b) Elongation- The codons in mRNA interacts with anticodon of tRNA and binds to it with the formation of peptide bond between -COOH group of first amino acid and NH2 group of second amino acid catalyzed by enzyme peptidyl transferase. This yields a long polypeptide chain as the ribosome move along the mRNA. (c) Termination- the termination of polypeptide is signalled by one of the three termination codons (UAA, UAG, UGA).

The gene battery model also proposes the occurence of 5 types of genes-producer, receptor, integrator, sensor and enhancer-silencer. Some of the basic type of genes are described below (a) Sensor genes-These genes are detectors as they are sensitive to the state of cell and its environment. These are responsible for sensing the need of an enzyme to be produced. (b) Interogator genes- These genes are associated with sensors, receive signals from sensors and transmit it to other genes. (c) Receptor genes- These genes receive signals from interogator genes and generally remain associated with the producer. (d) Producer genes- These genes are the output controls of the regulation merchanism.

This is how the gene expression levels play a significant role in the formation of final functional protein product from DNA itself in a typical embryo.