Cell Bio- Regulation Of Gene Expression

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Gene expression:

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Represents a process in which the genetic information saved in individual genes is converted into functional molecules of encoded proteins.

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Why is the expression of individual genes regulated within the cell?

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Because the effective functioning of organisms require the regulation of individual gene expression.

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Gene expression in unicellular organisms:

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Requirements for adaption to changed environmental conditions

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Gene expression in multicellular organisms:

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Requirements for selective expression of genes in order to achieve relevant differentiation status of various cells within the body. The expression of different genes leads to different cell types (cell differentiation)

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Levels of the regulation:

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1. Genome (DNA)
2. Transcription (DNA-> RNA/ primary transcript)
3. Post-transcriptional modifications (RNA/primary transcript-> mRNA)
4. Translation (mRNA-> polypeptide chain)
5. Post- translational modifications (polypeptide chain-> functional protein)
6. Protein degradation (functional protein-> degraded protein)

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Genome can affect expression of genes in several ways:

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1. Gene amplification
2. Genom rearrangement
3. Chromosome condensation/ decondensation
4. DNA methylation

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Gene amplification:

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The number of copies of certain genes are amplified

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Genom rearrangement:

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Transposons, genes coding immunoglobulins

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Chromosome condensation/ decondensation:

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Higher degree of condensation renders DNA less accessible for transcription factors and RNA polymerase (heterochromatin, X- chromosome). Histone deacetylase removes the acetyl group from histones--> DNA less accessible.

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DNA methylation:

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Enzyme methylase catalyse methylation of cytosine in DNA (5- methylcytosine). The degree of DNA methylation corresponds to the degree of gene expression. Genes with methylated DNA are generally not expressed (X chromosome, genomic imprinting)

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How is transcription usually regulated?

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By binding of specific proteins to specific sequences of DNA

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Regulatory DNA sequences:

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DNA sequences (10- 10 000 base pairs) involved in switching a particular gene on or of. Promotor, other regulatory DNA sequences)

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Gene regulatory proteins:

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Involved in regulation of gene expression by binding to specific regulatory DNA sequences. (General transcription factors, specific transcription factors)

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Gene regulatory proteins contain several types of DNA binding motives:

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- Homeodomain
- Zinc finger
- Leucine zipper

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The regulation of transcription in prokaryotic cells:

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- Operon: a cluster of genes transcribed from a single promotor
- Repressor & operator: binding site for repressor within promotor. Tryptophan operon
- Activator and binding site for activator- lac operon.

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The regulation of transcription in eukaryotic cells:

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General transcription factors assemble with RNA polymerase at the promoter of gene via binding to TATA- box. TATA- box is a DNA sequence within the promoter composed mainly of A and T.
- Activator & enhancer: binding site for activator, activation at a distance.
- Combinatorial control: Several regulatory proteins work together in order to control the expression of a particular gene

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Post- transcriptional modifications that affects expression of a particular gene:

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- RNA capping
- RNA polyadenylation
- Alternative splicing
- RNA editing

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Alternative splicing:

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It allows several proteins to be encoded from the same gene on the basis of differing exons of the gene employed to form mRNA. Different proteins are expressed from the same gene by different cell types during different stages of development.

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RNA editing:

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Is an insertion or deletion of nucleotides or a substitution of nucleotides in transcribed RNA. It means certain change of transcribed genetic information. It can result in the appearance of new initiation or stop codons

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How translation can affect gene expression?

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mRNA molecules are eventually degraded within the cell. The lifetime of a mRNA molecule affects the expression of a particular gene. (The longer lifetime of mRNA means higher lever of translated protein and vice versa). The lifetime of mRNA is regulated by nucleotide sequences in the 3`untranslated region of mRNA

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Translation can also be regulated by specific protein binding to mRNA. Example:

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IRP: iron regulatory protein
IRE: iron responsive element

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Post- translational modifications that affect gene expression: (7)

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1. Removal of methionine from the N-end: every newly synthesized polypeptide chain starts with methionine
2. Removal of signal sequence: the signal sequence is a sequence of amino- acids serving as a signal for transfer to required location
3. Proteolytic cleavage: the formation of functional protein by cleavage of a precursor polypeptide chain (proinsulin-> insulin)
4. Formation of disulfide bond: they are formed between adjacent cysteines. They help to stabilize protein structure
5. Chemical modification of amino- acids: Phosphorylation, hydroxylation.
6. Glycosylation: the binding of oligosacharides (glycoproteins)
7. Binding of prosthetic groups: (nonamino- acid/ nonprotein molecule) can be required for functioning of protein. (heme in hemoglobin)

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Protein degradation that can affect gene expression:

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Protein degradation is a way the amount of proteins within the cell can be regulated. Individual proteins vary in their lifespan. Most proteins are degraded by proteasome. Proteasome is a large complex of proteolytic enzymes forming a kind of a cylinder. Proteins are marked for degradation by the covalent binding of ubiquitin molecules which are small proteins