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