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6.1 Cellular Control, Chromatin remodelling is essential for controlling…

- - - - Body plan.
        
        The basic structured arrangement of an organism's parts, which are determined by genetic and developmental factors.
      - Homeobox Gene
        
        A group of regulatory genes with a conserved DNA sequence that guides the development of body plans.
      - Homeobox Sequence
        
        A highly conserved DNA sequence found within homeobox genes that is crucial for the development of an organism's body plan.
      - Hox Gene
        
        A subset of homeobox genes in animals, containing homeobox sequences essential for the correct positioning of body parts.
    - - Homeobox sequences encode the homeodomain, the part of a protein that binds to DNA.
      - The homeodomain operates as a transcription factor.
      - It binds to DNA, switching developmental genes on or off.
      - This modifies the transcription of proteins necessary for the development of body plans.
    - - The number of body layers.
      - The symmetry of the body.
      - The anterior-posterior axis, ensuring a head is at one end and any tail is at the other.
      - The segmentation of the body into head, thorax, abdomen, and so on.
      - The position and development of limbs, eyes, and other important structures.
    - - A mutation would have large effects by altering the organism's body plan.
      - Many other genes would also be affected by a mutation in a homeobox gene.
      - Mutations are likely to be lethal and selected against.
  - - - There are fewer ethical concerns than other animals.
      - They are low cost.
      - Their genetics and development are well understood.
      - They have a rapid reproduction rate.
      - They have a simple body plan.
      - Their mutations can be studied with a low-powered microscope.
  - - - Regulatory genes are able to respond to internal stimuli like stress, drugs, or hormones, which can cause DNA damage.
      - When DNA is damaged, regulatory genes trigger the cell cycle to stop and initiate apoptosis.
      - This prevents the DNA damage from being replicated into new cells.
    - - Regulatory genes can respond to external stimuli like changes in temperature or light intensity.
        For instance, a lack of nutrients may trigger cell division.
- - - - Addition of a 5’ cap - This stabilises the mRNA, delays its degradation, and assists in ribosome binding.
      - Addition of a 3’ poly-A tail - This stabilises the mRNA and delays its degradation.
      - Splicing - Introns are removed and exons are joined together, providing the instructions for the protein sequence.
  - - - These can bind to mRNA, preventing it from attaching to ribosomes.
      - This decreases translation and protein synthesis.
    - - mRNA that degrades slowly is more stable and lasts longer.
      - This can increase translation and protein synthesis.
    - - Activated initiation factors help mRNA bind to ribosomes.
      - This initiates translation and increases protein synthesis.
      - For instance, after fertilisation, initiation factors are activated, allowing the translation of stored maternal mRNAs.
    - - Protein kinases are a type of enzyme that can control many aspects of cellular activity, including protein modification
      - They do:
        
        Protein kinases add phosphate groups to proteins through phosphorylation.
        
        Phosphorylation changes the protein's tertiary structure and function.
        
        This often activates enzymes.
        
        The activity of protein kinases can be regulated by cyclic AMP (cAMP).
  - - - The addition of carbohydrates, lipids, or phosphate groups.
      - The formation of disulfide bridges between amino acids.
      - The shortening of peptide chains.
      - Folding into specific 3D shapes.
      - Modification by cAMP, as seen in the lac operon.
- - - - Transcription factors are proteins that bind to specific DNA sequences to initiate the transcription of genes into mRNA.
      - mRNA that is produced during transcription then carries the genetic code from DNA to ribosomes, allowing the production of proteins. Transcription factors therefore have a crucial role in gene expression regulation.
      - When a gene is 'switched off', transcription factors cannot bind to DNA. This prevents the transcription process and so the synthesis of polypeptides.
    - - Epigenetic regulation involves changes in gene expression without altering the underlying DNA sequence, such as through histone modifications. Histone modifications can influence chromatin structure and gene activity by making DNA more or less accessible for transcription.
      - Modifications that promote transcription include
        
        Acetylation
        
        This process involves adding acetyl groups to histones, decreasing their positive charge and resulting in a looser DNA coil and increased transcription.
        
        Phosphorylation
        
        Adding phosphate groups to histones also reduces their positive charge, resulting in a looser DNA coil and increased transcription.
      - Modification that inhibits transcription
        
        Methylation
        
        This involves adding methyl groups to histones, increasing hydrophobic interactions and tightening the coiling of DNA, which reduces transcription.
    - - Chromatin structure plays a significant role in gene expression in eukaryotic cells. Negatively charged DNA wraps around positively charged histone proteins to form chromatin.
      - Chromatin can exist in two forms:
        
        Heterochromatin
        
        This form of chromatin is densely packed, making it difficult for RNA polymerase to access genes, thus preventing transcription.
        
        Euchromatin
        
        This is a loosely packed form of chromatin that allows easy access for RNA polymerase, enabling active transcription of genes.
  - - - An operon is a cluster of genes controlled by a single promoter, allowing for coordinated expression. This system is particularly efficient in prokaryotes for regulating the expression of multiple genes simultaneously.
      - Operons consist of several key components:
        
        Regulatory Genes
        
        These encode proteins that regulate the expression of the structural genes.
        
        A Promoter Region
        
        This is the site where RNA polymerase binds to initiate transcription.
        
        An Operator Region
        
        This is a sequence where regulatory proteins (like repressor proteins) can bind.
        
        Structural Gene
        
        These genes code for proteins, typically enzymes.
      - The lac operon is a group of genes in the bacterium Escherichia coli that control the metabolism of lactose, allowing them to use lactose as an energy source when glucose is scarce. The genes are controlled by the same promoter region and are transcribed together.
      - The lacI regulatory gene of the lac operon codes for a repressor protein that can inhibit and control the lac operon's activity.
      - The lac operon includes three structural genes essential for lactose metabolism:
        
        gene: lacZ
        
        Enzyme: β-galactosidase
        Function: Breaks down lactose into glucose and galactose
        
        gene: lacY
        
        Enzyme: Lactose permease
        Function: Transports lactose into the cell
        
        gene lacA
        
        Enzyme: Transacetylase
        Function: Modifies lactose or its by-products
    - - When lactose is absent:
        
        1.The repressor protein binds to the operator region.
        
        2.RNA polymerase is blocked from the promoter region.
        
        RNA polymerase can't transcribe the structural genes.
        
        The enzymes for lactose metabolism aren't produced.
      - When lactose is present:
        
        1.Lactose binds to the repressor protein.
        
        The repressor protein changes shape and is released from the operator region.
        
        RNA polymerase can bind to the promoter region and initiate transcription.
        
        RNA polymerase transcribes the structural genes, leading to the production of enzymes necessary for lactose metabolism.
    - - Glucose is the preferred energy source for E. coli. The presence of glucose indirectly inhibits the lac operon via a signalling molecule, cyclic AMP (cAMP).
      - When only lactose is present:
        
        cAMP levels increase, and cAMP binds to the cAMP receptor protein (CRP).
        
        The CRP-cAMP complex upregulates the transcription of the lac operon.
        
        Lactose metabolism is optimised.
      - When both glucose and lactose are present:
        
        Glucose reduces cAMP levels.
        
        The CRP-cAMP complex cannot form.
        
        The lac operon's transcription is downregulated.
        
        Lactose metabolism enzymes are not produced.
      - Glucose presence, therefore, suppresses lactose metabolism in favour of the more efficient energy source.