BIO421Lecture 13

Advanced GeneticsFinish Proteomics,

Begin Epigenetics

  1. Epigenetics
  2. What is the definition of epigenetics?
  3. We will watch a video with the leaders in epigenetics talking about the definition
  4. Alteration of DNA and histones without changing the DNA sequence
  5. Heritable changes that are passed down during cell division
  6. Changes are reversible
  7. Epigenetic changes to chromatin – shuts down gene expression
  8. DNA methylation
  9. Methyl groups added to 5’ carbon of purine ring of C nucleotides
  10. Histone modification – makes nucleosomes tighter and less accessible to transcriptional machinery
  11. Methylation of specific lys and arg residues
  12. De-Acetylation
  13. Examples of Epigenetic alterations.
  14. Dosage Compensation - For some of the genes present on the X, the amount of protein produced is critical, and the same needs to be expressed in male and female embryos.
  15. XIST and TSIX genes compete to turn off one X chromosome in human embryos
  16. One X chromosome becomes coated with XIST RNA, and it condenses. Each time this chromosome is replicated, the condensation pattern is conserved.
  17. Transposon silencing
  18. Transposons jump around in the genome, damaging the DNA strands
  19. Three mechanisms are used to silence them

1)DNA methylation

2)Histone methylation

3)RNA interference

  1. Genomic Imprinting by Methylation
  2. Equivalence of pronuclei

1)Sperm and egg pronuclei are not equivalent

(i)Results of nuclear transplant experiments

2)Different genes are "turned off" in each pronucleus

3)Gene inactivation is due to methylation

(i)mechanism of methylation: methyl group added to C in CG dinucleotides

4)Referred to as genomic imprinting

  1. Examples of genes that are imprinted:

1)Igf2 and Igf2R.

(i)Represents intragenomic conflict in the embryo.

  1. As the embryo develops, more loci become methylated.
  2. Evolutionary arms race between male and female pronuclei
  1. Micro RNAs
  2. The first miRNA: lin-4 in C. elegans
  3. Discovered through mutational analysis
  4. very hard to identify the mutated gene
  5. did not encode for a protein
  6. Seemed to have an antagonistic relationship with lin-14
  7. lin-14 function favors early cell fates
  8. lin-4 function favors older cell fates
  9. lin-4 encodes an RNA that forms a small stem loop, which matches the 3’UTR of lin-14.
  10. the RNAi machinery cleaves the stem loop and destroys the lin-14 mRNA
  11. there are many mathing sites for lin-4 in the lin-14 3’UTR
  12. Many more miRNAs were discovered in all eukaryotes
  13. Most miRNAs bind to multiple transcripts
  14. Most transcripts regulated by miRNAs bind more than one miRNA