Epigenetics

Question 1

What is epigenetics?

Answer 1

the study of changes in organisms caused by modification of gene expression rather than alteration of the genetic code itself
Does not alter the underlying DNA sequence.

Question 2

How does chromatin structure play a role in gene expression?

Answer 2

• A more open chromatin stucture - more permissive to gene expression
• Modifying histone packaging of DNA can modify gene expression

Question 3

How does nuclei structure affect gene expression?

Answer 3

• Tightly packed DNA in nucleus = areas where gene is not expressed (heterochromatin)
• Chromatin : heterochromatin ; tightly packed DNA, not transriptionally active euchromatin ; less tightly packed, site of active transcription

Question 4

What is DNA methylation?

Answer 4

• DNA methylation works by adding a chemical group to DNA. Typically, this group is added to specific places on the DNA, where it blocks the proteins that attach to DNA to “read” the gene
• High methylation = more closed chromatin confromation = Gene switched off
• methylation depending on our development from embryo to adult
• Low methylation in embryonic cell compared to an adult cell
• During development, methylation varies

Question 5

What are the parental specific contributions to development?

Answer 5

• Gynogenegtic embryos = retarded growth / developement of extraembryonic tissues
• Androgenetic embryos have retarded growth/ devolopment of embryonic tissues

Question 6

What are imprinted genes?

Answer 6

• the process by which only one copy of a gene in an individual (either from their mother or their father) is expressed, while the other copy is suppressed.

Question 7

What are non-coding microRNAs?

Answer 7

• Small post-transcriptional gene silencing RNA interference molecules.
• Transcription of primary transcript (Pri-miRNA ; 1KB)
• Folds omtp a stem loop structure prior to cleavage by Drosha/ DGRC8 pre-miR
• Further cleavage by Dicer to yield an ~ 20bp mature miR
• After loading onto the RNA-induced silencing complex (RISC), the miR is able to disrupt RNA translation or induce degredation

Question 9

What is X chromosome inactivation?

Answer 9

• X chromosome contains over 1,000 genes that are essential for proper
  development and cell viability.
• Females carry two copies of the X chromosome, resulting in a potentially
  toxic double dose of X-Iinked genes.
• Mammalian females randomly inactivate one of their X chromosomes
• The inactivated X chromosome then condenses into a compact structure
  called a Barr body, and it is stably maintained in a silent state
• Regulated by a noncoding RNA called XIST.
  X Chromosome Inactivation
  c
• The XlSTgene does not encode a protein but rather produces a 17 kb RNA molecule.
  XIST RNA is only expressed in cells containing at least two Xs
• During X chromosome pairing, a counting mechanism dictates that only one X per cell can remain
  active. In such cells, XlSTis expressed from all supernumerary Xs.
• XIST RNA remains exclusively in the nucleus and is able to “coat” the chromosome from which it was
  produced.
• Paradoxically, XISTRNA is expressed from an otherwise inactive X chromosome.

Question 10

What is the process of modification to histone tails?

Answer 10

• Stone proteins form the core of the nucleosome. 2.5% of each histone forms a tail which protrudes from the nucleosome
• Modification to the histone tails can alter the interactions between histones and Dna, opening or closing the DNA
• Histone modifications can impact gene expression by altering chromatin structure or recruiting histone modifiers
• Histone acetylates (HDACs ) catalyse the removal of acteyl hroups from histone lysine residues
• Histone acetyltranserases (HATs) add acetyl groups onto the histone tails.

Question 11

What is somatic nuclear transfer (SNT)?

Answer 11

• Can be used to make embryonic stem cells that match the donors genetic makeup for therapeutic purposes
• Patient derived SCNT-ESCS could be directed to differentiate into specific lineages that could be used to treat or study diseases , i.e.e neurons for Parkinson’s or Alzheimer’s disease
• As they would be patient-derived, there is no risk of immune rejection as in conventional transplantation
• Not routinely used due to low efficiency, ethical issues using oocytes and the devlopment of IPSCS

Question 12

What is ESC fusion?

Answer 12

• ESCS and somatic cells are forced to fuse ( either using viral, chemical or electric cell fusion approaches)
• If fused cells proliferate, they will become hybrids. Upon diviision, cells can contain multiple copies of the genomes, or can incorporate aspects of both cells
• Can push the amount of desired cells you get throgh manipultaing the culture media to contain specific factors

Question 13

What is epidgenome editing?

Answer 13

• Utilising genome editing tool, such as CRISPR-Cas9 , Zinc finger and TALENs, to modify key epigenetic players.