Gene Regulation in Eukaryotic Cells PDF

G E N E R E G U L A T I O N I N E U K A R Y O T I C C E L L DR L MAKUL ANA Introduction to gene regulation in eukaryotic cell The control of gene expression in eukaryotes is a complex and multi-layered process that ensures genes are expressed at the right time, in the righ...

G E N E R E G U L A T I O N I N E U K A R Y O T I C C E L L DR L MAKUL ANA Introduction to gene regulation in eukaryotic cell The control of gene expression in eukaryotes is a complex and multi-layered process that ensures genes are expressed at the right time, in the right cell type, and the appropriate amounts. This regulation is crucial for development, differentiation, and response to environmental stimuli. Introduction to gene regulation in eukaryotic cell Different cell types (liver, pancreatic or stem cell) share the same genome (DNA sequence) but differ in their epigenomes, the packaging and modification of this genome Eukaryotic genes are not generally organised into operons, genes that encode proteins are scattered within the genome Similarity: Activator and repressor proteins that recognize specific DNA sequences are central to many gene-regulatory processes. Transcription factors in gene regulation The roles of eukaryotic transcription factors (TF) are different in several ways 1. DNA-binding sites in eukaryotes are further away from the promoter 2. Expression of each gene controlled by multiple TF 3. Some TF interact directly with RNA polymerase (RP) while many others interact indirectly TF HAS SEVERAL DOMAINS  Mediator is a giant complex with different subunits 20 in yeast and 30 in human This subunits are referred to as MED proteins Mediator is a crescent-shaped protein with a head and middle regions and tail Tail binds to co-activators or co- repressors bound to enhancer and silence elements. Head and middle bind to CTD of RNA polymerase II Middle also binds to general transcription factor TFIIE Features shared in common 1.They are often redundant 2.They are modular 3.They can act synergistically  The control of gene expression can require chromatin remodelling Chromatin is composed of DNA wrapped around histone proteins, forming nucleosomes, the basic units of chromatin. These nucleosomes can be tightly packed (heterochromatin) or loosely packed (euchromatin), influencing whether genes are turned on or off.  Demonstration of chromatin remodelling in gene expression Genes required for galactose utilisation in yeast are activated by a transcription factor called GAL4 GAL4 recognises DNA-binding sites with two 5’ –CGG-3’ Approximately 4000 potential GAL4 binding sites are found in yeast genome Only 10 of the 4000 regulate genes needed for galactose metabolism.  How is GAL4 targeted to only a small fraction of the potential binding sites? The chromatin immunoprecipitation was done to study this In the absence of galactose The heterochromatin structure In the presence of galactose Chromatin remodelling occurs favouring the Euchromatin structure  Chromatin remodelling through acetylation Histone acetylation usually lysine residues by histone acetyltransferases (HATs) The interaction of the lysine with DNA results in euchromatin structure  Chromatin remodelling through methylation DNA methylation occurs at cytosine residues in CpG islands Highly methylated DNA are associated with gene expression Eukaryotic gene expression can be controlled at posttranscriptional levels Iron metabolism RNA secondary structure is crucial Iron is an essential nutrient in the synthesis of haemoglobin, cytochromes and many other proteins Excess Iron is harmful – initiates a range of free-radical reactions that damage proteins, lipids and nucleic acids Iron metabolism Iron-Responsive Elements (IREs) IREs are specific RNA sequences that form stem-loop (hairpin) structures. These elements are typically located in the untranslated regions (UTRs) of mRNAs involved in iron metabolism, such as those encoding ferritin (an iron storage protein) and the transferrin receptor (TfR, which imports iron into cells).  Iron metabolism Iron-Responsive Elements (IREs) The IREs function as binding sites for Iron Regulatory Proteins (IRPs), which are RNA-binding proteins that respond to cellular iron levels... The binding of IRPs to IREs is crucial for regulating the stability and translation of the mRNAs that control iron homeostasis. Iron Regulatory Proteins (IRPs) IRP1 and IRP2 are the two main IRPs in mammals. Their activity is regulated by the cellular iron levels: Low iron conditions: IRPs bind to the IREs in mRNAs, influencing their translation and stability. High iron conditions: IRPs undergo conformational changes or degradation, reducing their ability to bind IREs, which alters the expression of iron metabolism genes.  NOW LET’S WRITE THE QUIZ AT 10:30