Chromatin Structure Flashcards
How is DNA organized?
into hierarchies of chromatin structures to form chromosomes
What is chromatin?
refers to the combination of proteins (histones) and DNA to comprise chromosomes; also RNA or other proteins
What are histones?
DNA binding proteins that compact the chromosomal DNA
What a histones rich in?
lysine and arginine that are positively charged to stabilize the DNA-histone interaction
How many times does DNA wrap around histone?
wraps 1.8 turns around the octamer in a left handed manner to form a nucleosome
What are the four core histones?
H2A, H2B, H3, and H4 (2 of each)
What is the function of the H3-H4 tetramer?
associates with DNA
What is the function of the H2A-H2B dimers?
associate to form the octamer
What is the core nucleosome?
about 146 bp of DNA wrapped around the octamer
What happens after the octamer is removed?
leaves the DNA negatively supercoiled (left handed)
What is the function of negative supercoiling?
facilitates strand separation
What is the function of histone tails?
- regulate nucleosome packing and interactions and chromatin structure and function
- interact with other nucleosomes to compact DNA further
What does each histone have?
an N-terminal “tail” that extends outwards between the DNA coils
How long are histone tails?
up to 25 amino acids in length and have an undefined structure
What is the function of H2A.X?
phosphorylated at sites of DNA double-strand breaks and is thought to recruit repair machinery
What is the function of CENP-A?
replaces histone H3 in nucleosomes at the centromere
What is the first level of chromatin compaction?
the 10nm fiber, which arises from nucleosome association with DNA, and has a “beads on a string” appearance; nucleosomes are separated by “liner region” of 20-60 bases; 10nm is folded further into 30 nm fiber
What is H1?
a linker histone that binds to the linker DNA in between successive nucleosomes, helping compaction of the 30 nm fiber; then compacted further into compact chromosomes in which large looks of chromatin are anchored to a central scaffold
What happens to the compaction in interphase?
when chromosomes are relatively uncondensed and genes are being transcribed, there is a range of compaction along the chromsome
What are euchromatins?
relatively decondensed regions stains lightly
What are heterochromatins?
more compacted regions stain more darkly
What are examples of heterochromatin?
- telomeres (special DNA at the ends of chromosomes) and centromeres
- regions with highly repetitive DNA sequences
How does chromatin structure affect cellular processes?
- rearrangements that place an origin of replication into heterochromatin result in late replication
- recombination involves breaking DNA and joining it to a different molecule. Heterochromatic regions experience less recombination, which can protect the genome
- CENP-A is needed to form a functional centromere, which is needed for proper chromosome separation
What are histone side chains subject to?
modification that act as signals during regulation: acetylation, methylation, phosphorylation, and ubiquitylation
What are the affects of modification?
- recruit specific proteins
- unstructured histone tails
What is the function of histone acetyltransferases (HATs)?
add acetyl groups to lysine side chains
What is the function of histone deacetylases (HDACs)
remove the acetyl groups
What is the function of methytransferases (HMTs)?
add methyl groups to lysine and arginine side chains
What is the function of histone demethylases?
remove the methyl groups
What is the function of acetylation?
- removes the positive charge from lysine side chains, affects interactions with negative DNA
- generates binding sites for bromodomain proteins, bind specifically to acetyl-lysines
What is the function of bromodomains?
recruit other proteins like nucleosome remodeling complexes
Euchromatin has _ acetylation than heterochromatin?
more
How many methyl groups can be added to a lysine?
three methyl groups
How many methyl groups can be added to an arginine?
two methyl groups
What is associated with silent chromatin?
methylation of lysine 9 in the H3 tail
What is associated with active chromatin?
methylation of H3 lysine 4
What is the function of chromodomains?
bind to specific methylated lysines, and are often associated with transcriptional silencing
What allows cell growth?
phosphorylation of H3 serine 10
What allows for chromosome condensation?
phosphorylation of H3 serine 10 and serine 28
What is histone code?
unique combinations of modification that define certain chromatin states
What does chromatin packing present?
a barrier to proteins that need to access DNA, and hence inhibits processes like transcription
ATP-dependent nucleosome remodeling complexes increase the accessibility of DNA by:
- sliding the histone octamer along the DNA
- removing the histone octamer and transferring it elsewhere
- introducing loops into the DNA
What are the functions of boundary elements?
- act as physical barriers to heterochromatin
- can be specific sequences to which proteins bind that are regulators of histone modifications
When do heterochromatin stop spreading?
until a boundary element is reached (H3 is deacetylated, lysine 9 is methylated, and a chromatin silencing protein binds)
What are chromatin loops?
each loop contains one type of chromatin, and the loop is anchored in the nuclear periphery which is another boundary element
