knowledge-23 GE

• Epigenetics is the study of the change in organisms caused by the modification of gene expression in eukaryotes. It involves heritable changes in gene function without changes to the base sequence in DNA.
• Inhibiting transcription:

  • increased methylation (addition of methyl ) of DNA, especially cytosine
  • Increased acetylation (addition of acetyl) of histone proteins associated with DNA.
• Methyl groups or "tags" inhibit transcription by changing the shape of DNA and making DNA inaccessible to transcription factors.
• Acetyl groups increase the expression of a portion of DNA by increasing transcription.
• the alteration of epigenetic process can lead to the development of diseases such as cancer.
• A disease caused by incorrect DNA methylation could be treated with drugs that contain enzymes that inhibit methylation.
• Diagnostic tests can be developed that detect cancer causing DNA methylation before symptoms present.
• Epigenetic mechanisms are effected by these factors and processes:

  • development
  • environmental chemicals
  • drugs
  • aging
  • diet
• DNA methylation:

  Methyl group can tag DNA and activate or repress genes.
• DNA acetylation:

  Acetyl groups can tag histone tails and cause expression of more genes by increasing transcription.
• DNA:

  Histones are proteins which DNA can wind for compaction and gene regulation.
• Histone modification:

  The binding of epigenetic factors to histone tails alters the extent which DNA is wrapped around histones and availability of genes in the DNA to be activated
• Transcription factors move from the cytoplasm into the nucleus to stimulate or inhibit transcription of target genes.
• Transcription factors bind to specific regions of DNA and regulates transcription , these binding sites can be blocked by an inhibitor thereby switching on or off the target gene.
• Estrogen is a steroid hormone can initiate transcription , it binds to complementary receptors on a transcription factor leading to its activation.
• once estrogen activates the transcription factor a inhibitor molecule is released from the DNA binding site on the transcription factor. this transcription factor can then move into the nucleus and bind with DNA , initiating transcription of particular genes.
• RNA interference inhibits the transcription of mRNA produced from target genes.
• Small interfering RNA (siRNA) are small, double stranded sections of RNA that combine with an enzyme and guide it to an mRNA molecule. One of the two strands of siRNA bind to a complementary section of mRNA and the enzyme cuts mRNA into smaller sections.
• mRNA cut into smaller sections is unable to be translated into a polypeptide , and the gene it codes for remains unexpressed.
• Using genome projects :

  • identifying potential antigens for use in vaccine production.
  • the presence of non-coding DNA and regulatory genes means that the sequence of nucleotides in a gene cannot be easily converted into the amino acid sequence in a protein.
• Gene mutations:

  a gene mutation is a change in the amount or arrangement of DNA in a gene. Gene mutations might arise during DNA replication.
• gene mutations occur spontaneously however the rate of mutation is increased by mutagenic agents such as ultraviolet radiation. Mutagens cause damage to DNA by removing groups such as NH2 , from nucleotides or adding groups to nucleotides.
• Some mutations can cause a change in a triplet code , causing a different amino acid sequence in the encoded polypeptide. this can result in the protein becoming non-functional.
• not all mutations cause changes to the encoded amino acid - these are called silent mutations.
• some gene mutations result in a frame shift such as addition or deletion. A frame shit is where the entire base sequence is shifted to a different sequence of amino acids.
• addition:

  • the addition of one or more nucleotides , resulting frameshift to the right. An addition of three bases will not cause frameshift but insertion of a new amino acids.
• Totipotent:

  • occur only for a limited time in early mammalian embryos
  • Can differentiate to produce any type of body cell , including placental cells
• pluripotent:

  • found in embryos
  • can differentiate into all tissue types except placental cells.
• Multipotent:

  • found in many tissue at any post-embryonic life stage
  • Can differentiate to form a limited number of different cell types
• one type of unipotent stem cell differentiates into cardiomyocytes . These unipotent stem cells are cardiac stem cells and only have the ability to become heart cells , to replace damaged cells.
• Cardiomyocytes are the main type of cell found in the heart. They ensure the heart contracts to pump blood around the body.
• Induced pluripotent stem cells are pluripotent cells produced from unipotent stem cells.
• The unipotent cells can be almost any body cell , and they are genetically altered to acquire the characteristic of an embryonic stem cell.
• Proto-oncogenes are genes that stimulate normal cell division they can mutate into oncogenes which cause tumor growth.
• Oncogenes code for a growth factor which is produce in excess, this growth factor activates cell surface membrane receptors which stimulate cell division in the absence of growth factors.
• Tumor suppressor genes:

  • genes that inhibit cell growth
  • if mutated they no longer inhibit cell division . the cell may die or continue to divide to form a tumor