Biology 305 - Epigenetics
Development can be controlled by antagonistic action of ____ and ____.
- TrxG (recruits HATs & opens chromatin) - PcG methylates (recruits HDACs & closes chromatin)
Adding _____ groups opens chromatin fiber (HATs). Neutralizes charge of ______. Increases _______.
- acetyl - lysine (K) - transcription (is reversible by actin of deacetylases - HDACs)
Facultative heterochromatin is _____ but can be _____, reversibly _______ genes, developmental and cell-type specific genes.
- closed - opened - repressed
Constitutive heterochromatin is _____, _______ repressed genes, repetitive elements.
- closed - permanently
Structural heterochromatin is _____ and used to organize ___.
- closed -DNA
Chromatin typically exists in which four types of states?
- euchromatin - facultative heterochromatin - constitutive heterochromatin - structural heterochromatin
New nucleosomes may slightly _____ (or ______) region of heterochromatin when they form on daughter helices.
- expand - contract
Adding _____ groups can be activating or ______ (HMTs).
- methyl, silencing (is reversible by removing methyl groups - HDMTs)
C bases, particularly with an adjacent G (CpG), can be ______. DNA ________ are recruited to CpG islands. - Once established, state is ______. - State can be passed on between ______.
- methylated - methyltransferases - maintained - generations
Euchromatin is ____; constitutive & _____ genes; cell-type.
- open - inducible
Methylation of DNA leads to ______ of genes. Can bring in ______ remodelers that close DNA.
- silencing - chromatin
After replication, new strand of DNA is _______. Pattern of _____ on old strand is copied to the new.
- unmethylated - methylation
If histones are not methylated, proteins like ____ cannot bind.
HP-1
Histones can be modified, generally on _-_______ tail amino acid.
N-terminal
Modifying enzymes can be brought in by ____.
RTFs
Trithorax group (TrxG) proteins lead to...?
activation
How does chromatin state of DNA get "remembered"?
because of what happens during DNA replication. - nucleosomes are broken up as the replisome passes through - regions that are compacted are generally passed on to daughter helices - association of DNA with nucleosomes is non-specific
Nucleosomes are made ________, using a mix of old and new.
dispersively
E(var) mutants show ________ variegation. (more heterochromatin spread)
enhanced
What is a level of inheritance beyond classical genetics?
epigenetics
Regulatory proteins can be readers, writer, or _______.
erases
Marks on histones are _________. (mostly, in mitotic divisions)
inherited
Marked histone tails can be a ______ ____ for other proteins.
landing spot
Variegated eye color is an example of chromatin _______.
modulation
Additional mutations in var strains show...?
more genes involved
Modified histones are read as a signal to modify...?
new (i.e., unmodified) histones in similar fashion - after DNA replication - net effect is for daughter helices to have same kind of nucleosomes as parent helix
Histones bind ___-_______ to DNA.
non-specifically (neg charge)
Histones are ________ charged.
positively
If HP-1 mutant suppresses variegation, w.t. HP-1 must...?
promote heterochromatin
Polycomb group (PcG) proteins lead to...?
repression
What are histones?
small, basic proteins
Su(var) mutants show _______ variegation. (less heterochromatin spread)
suppressed
Explain example of IGF2/H19 gene expression.
• on maternal chromosome, H19 is on and IGF2 is off • insulator protein binds to imprinting control region (ICR) • insulator blocks activation of IGF2; allows transcription of H19 • on paternal chromosome, H19 is off and IGF2 is on • ICR is methylated & insulator cannot bind • methylation blocks H19 but allows activation of IGF2 • in diploid cells, only one copy of each gene is active • for mutants, it matters which parent contributed the mutation!
What are the steps of classical forward genetics?
• start with screenable trait, eye variegation in this case • find (or make) mutants that alter that trait • map mutations • each mutation mapping to a different locus identifies another gene involved • follow up with sequencing, cell biology, biochemistry, etc