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Control of Gene expression Eukaryotes (Enhancers and specific…
Control of Gene expression Eukaryotes
Gene expression control
Genes encode proteins and it is the proteins in the cell that dictate cell function
Thousands of genes expressed in a particular cell determine what cell can do
Each step in the flow of infomation from DNA to RNA to provides the cell with a potential control point for self-regulating functions
Gene --Transcription--> pre-mRNA --RNA processing--> mRNA --Translation--> Protein --Post translation --> Functional protein
Transcription active chromatin is structurally distinct from inactive chromatin
Chromotin is the DNA- Protein complex which comprises eukaryotic chromosomes
Ekaryotic Chromosomes
Linear DNA molecules associated with protein
Chromotin is DNA wound around clusters of eight histone proteins (Octamer)
Histones not only keep DNA organised but they are also known to help regulate expression of genes
RNA polymerase 1 - resides in the nucleus
Histone acetylation is the addition of an acetyl group -COCH3 to the histone tail
Lysine groups are acetylated they are neutralised and histone tail no longer binds to neighbouring nucelosome
Makes structure less compact and more accessible to transcription
Decatylation - removes the acetyl group and the promotes folding
Histone methylation
addition of a methyl group to the histon tail
Reduced transcription
Might block DNA access to transcription factors, while the histone acetylation might change electrostatic interactions within the chromatin ti open up DNA and allow transcription
Addition of a phosphate group amino acid to the methyl group can have the opposite effect
DNA methylation
Addition of a methyl group to certain bases in DNA
Can cause long tern inactivation of genes in cellular differentiation
In genomic imprinting, methylation regulates expression of either the maternal or paternal alleles of certain genes at the start of development
Epigenetic inheritance: Although chromatin modification do not alter DNA sequence, they may be passed to future generations of cells
The inheritance of traits transmitted by mechanisms not directly involving the nucleotide sequence is called epigenetic inheritance
Chromatin-modifying enzymes provide initial control of gene expression by making a region of DNA either more or less able to bind the transcription machinery
To initiate transcription, eukaryotic RNA polymerase requires the assistance of proteins called transcription factors, they cannot initiate transcription on their own
Enhancers and specific transcription factors
Proximal control elements are located close to the promoter
Distal control elements, groups of which are called enhancers
An activator is a protein that binds to an enhancer and stimulates transcription of a gene
Bound activators cause mediator proteins to interact with proteins at the promotor
Can function as repressors- inhibiting expression of a particular gene
Transcription factors are regulated by signals produced from other molecules: Hormones can activate transcription factors and thus enable transcription, they can therefore activate certain genes
RNA processing
the 5' cap and the poly A tail are involved in the regulation of translation efficiency and message stability
Facilitate the export of the mature mRNA from the nucleus - tracked
Help protect the mRNA from degradation by Hydrolytic enzymes
Help ribosomes attach to the 5' end of the mRNA
mRNA degradation
Levels of mRNA in the cytolplasm determines the level of encoded protein product
levels are regulated by rate synthesis, export and degradation
Controls level of gene expression
have longer half life in cell. mRNA encoding signalling proteins shorter.
differences are partially mediated by structural characteristics of transcripts
Indicated that sequences within 5' untranslated regions and 3; were the primary determinants of rapid mRNA decay - due to affinity for ribonucleases
Alternative splicing
During RNA splicing, exons are either retained in the mRNA or targeted for removal in different combinations to create a diverse array of mRNAS from a single pre-mRNA
Cancer and inherited diseases in humans are associated with this
Translation
Another opportunity to control gene expression - poly A tail and 5' cap are required for ribosome bending
Poly A tail = stimulation of translation initiation = this involves an interaction between the cytoplasmic poly A binding protein covering the poly A tail, and the translation initiation factor F4G bound to the 5 cap as part of the elF4F complex
Protein processing and degradation
Final opportunity for controlling gene expression
They may be cleaved, acquire sugars/phosphate group
Polypeptides often must be transported to specific destination in the cell to function