Lecture 27 Flashcards
where do histone modifications occur?
on N-terminal ends of core histones that protrude from nucleosome
4 examples of histone modifications
- acetylation
- methylation
- phosphorylation
- ubiquitination
3 types of histone modifiers
- Writers
- Erasers
- Readers
what are readers?
can recognize and bind modifications –> coupled with writers and erasers –> 1 mark is made which recruits a reader to allow more marks by the associated writer
how does histone acetylation increase transcription? (2)
- lysine is acetylated to neutralize its (+) charge
- loosens its interactions with (-) DNA
- chromatin relaxes, more accessibility, more transcription - makes binding site for histone code readers that promote activation
what is the writer enzyme for histone acetylation?
HAT
what proteins typically have HAT activity?
transcriptional co/activators have HAT activity
what is the eraser enzyme for histone acetylation?
HDAC
what proteins typically have HDAC activity?
transcriptional co/repressors have HDAC activity
how does histone methylation reduce transcription? (2)
- lysine or arginine is methylated (charge is unaffected) to silence genes
- makes binding site for histone code readers
what is the writer enzyme for histone methylation?
HMTase
does histone methylation promote heterochromatin or euchromatin formation?
heterochromatin
how does histone methylation promote heterochromatin formation? (4 steps)
- Heterochromatin Protein 1 (HP1) binds methylated histones (H3K9Me)
- HP1 induces methylation formation and recruits more HMTase
- HMTase methylates neighbouring nucleosomes which become new HP1 binding site
- heterochromatin spreads!
what stops the spread of heterochromatin?
- HATs bind a barrier insulator DNA seq
- this causes acetylation to counteract the spread of heterochromatin (i.e. sets limit for where heterochromatin is)
definition of epigenetics
study of heritable traits that are not explained by changes in DNA sequences due to proteins associated with DNA
can epigenetics be inherited?
yes, can be passed to daughter cells in mitosis
how do epigenetics marks get inherited in mitosis?
- during DNA replication, nucleosomes disassemble to let replication fork pass thru
- then, nucleosomes reassemble on daughter strands as a mix of new and old histones
- old histones with modifications recruit readers and writers for modifications of new histones
what is the phenomenon that occurs in Drosophila due to epigenetic modifications?
Position-Effect Variegation
what is the gene involved in position-effect variegation?
white gene –> ABC transporter that brings red pigment to eye
WT = red pigment
mutant = white pigment
what chromosome is the white gene found on?
X chromosome
describe a normal, WT drosophila eye
there is a barrier insulator, where part is heterochromatin and the other part is euchromatin
- the WT white gene is in euchromatin so it is expressed normally and the eye is fully red
describe a drosophila eye with position-effect variegation
mutagenized with X-rays –> creates inversions where white gene is close to heterochromatin
the barrier insulator has moved, so the heterochromatin can randomly spread into the white gene
–> in some cells, there will be more heterochromatin spreading so the gene will be silenced (white)
–> in other cells, there will be less heterochromatin spreading so the gene will be expressed (red)
all cells have the same genotype but different amounts of heterochromatin
what is non-mendelian genetics?
traits don’t segregate according to Mendel’s law –> genotype =/= expected phenotype
when does dosage compensation occur?
in FEMALE mammalian embryo at 8-32 cell stage
what is dosage compensation?
each cell randomly inactivates one of the X-chromosomes and forms a heterchromatic Barr body
what is the purpose of dosage compensation?
allows males and females to have equal expression of genes on the X chromosome
why do all descendent cells have the same inactive X chromosomes as the parent cell?
epigenetics are inherited in mitosis