Lec 02- DNA Chromosomes and Genomes 2 Flashcards
What is epigenetics?
a form of inheritance that is superimposed on the genetic inheritance based on DNA
What are 3 examples of epigenetics?
- DNA methylation
- Chromatin structure
- Histone modification
What are the 3 challenges to the idea that histones are thought to just be involved in packaging of DNA?
- Mammalian chromatin contains equal mass of histones and non-histone proteins
- Histones are highly conserved
- Heterochromatin silences the genes it packages without regard to sequence and is directly inherited by daughter cells
What does heterochromatin do?
- silences the genes it packages without regard to sequence
- is directly inherited by daughter cells
What suggests that histones have other functions besides purely structural?
other proteins bind to histones
How many amino acid differences are there between mammals and peas?
only 2 amino acid differences on H4
any change = deleterious
Heterochromatin characteristics
- chromatin that is very condensed
- stains darkly throughout the cell cycle (even in interphase)
- late replicating
- genetically inactive
- very few genes
The genes that are present on heterochromatin are resistant to ________
gene expression
Where is heterochromatin highly concentrated?
at centromeres and telomeres
What is position effect?
activity of a gene depends on position on the chromosome
What happens if a gene’s position is relocated near heterochromatin?
- it will be silenced
- zone of inactivation spreads a different distance in different cells
What is euchromatin?
all the rest of chromatin that is less condensed than heterochromatin
What kind of modifications are the amino acid side chains of histones subject to?
covalent modifications
Where do covalent modifications of histones occur?
histone core and tail
Acetylation of lysine characteristics
- loosens chromatin structure
- added by histone acetyl transferases (HATs)
- removed by histone deacetylase complexes (HDACs)
Characteristics of Mono, Di, and Tri-methylation of lysines
- Added by methyl transferases
- Removed by histone demethylases
What covalent modifications occur with histones?
- Acetylation of lysine
- Mono, di-, tri-methylation of lysine
- Phosphorylation of serine
What does the recruitment of the histone covalent modification enzymes depend on?
gene regulatory proteins
Are histone modifications reversible?
yes, but can persist long after regulatory proteins have disappeared
What determines how/when/if gene expression takes place?
the types of proteins the modified DNA attracts
Varient histone proteins exist for each core histone except which?
H4
Varient histone proteins are present in ___________ amounts than core histones and are __________.
much smaller amounts
less well-conserved
When are major histones synthesized?
during S-phase
What are major histones assembled into?
nucleosomes on daughter DNA helices just behind the replication fork
When are variant histones synthesized?
during interphase
What are variant histones inserted into?
already-formed chromatin
What do varient histones require?
histone exchange process catalyzed by chromatin remodeling complex
Histone code characteristics
- has specific meaning for cell
- determines how/when DNA is packaged in nucleosome
How is the histone code read?
by the code reader complex
What does the code reader complex involve?
joint recognition of histone tail and covalent modifications
Histone code can ________ as the cell needs change
change
What happens after modifying enzyme marks one or few neighboring nucleosomes?
chain reaction can ensue
What enzymes spread the mark over the chromosome?
the code reader-writer enzyme
What do the code reader-writer complexes also contain?
an ATP-dependent chromatin remodeling protein
All the chromatin remodeling complexes work together to _________
either condense or decondense long stretches of chromatin as the reader moves along
What 2 mechanisms halt the spread of chromatin modifications?
- physical barriers
- enzymatic barriers
What does the HS4 region on the chromatin do?
-protects the b-globin locus from silencing
What cluster does the HS4 rein on chromatin contain?
cluster of histone acetylase binding sites
What does the centromeric heterochromtin contain which makes it special?
- centromere-specific H3 histone
- CENP-A
- other proteins that pack the nucleosomes into dense arrangements to form kinectochore