Genet 302 lec 33 & 34
What is a nucleosome?
DNA wrapped around a histone octamer
What proteins make up the core histone octamer?
2 copies each of H2A, H2B, H3, and H4
What is histone H1 associated with?
Linker DNA
What is one major function of histone proteins?
To compact DNA so it fits inside the nucleus
Why can histones bind DNA well?
Histones are mostly positively charged and DNA is negatively charged
What is another major function of histones besides DNA compaction?
They can block promoters as a form of gene regulation
How can histones regulate gene expression by blocking promoters?
If a promoter is wrapped too closely around a nucleosome, transcription machinery cannot access it well
What are histone variants?
Alternative histone proteins that can replace regular histones in some nucleosomes
What human histone variant is associated with the inactive X chromosome?
MacroH2A
What histone variant is associated with centromeres?
CENP-A, also called CenH3 in some lectures
What are histone modifications?
Small organic groups covalently and reversibly added to amino tails (8)- temporaily modified
Which amino acids were emphasized as common targets for histone modification?
Lysine, arginine, and serine
What are the 3 major histone modifications emphasized in this lecture?
Acetylation- lysine, methylation- arginine, and phosphorylation- serine
What does H3R17me mean?
Histone H3, Arginine 17, methylated
What does H3K4me mean?
Histone H3, lysine 4, methylated
What does H3S10ph mean?
Histone H3, serine 10, phosphorylated
What are writers in chromatin biology?
Enzymes that add histone modifications
What are erasers in chromatin biology?
Enzymes that remove histone modifications
What are examples of histone writer and eraser enzymes for acetylation?
HATs (histone acetyltransferases) add acetyl groups and HDACs (histone deacetylases) remove them
What does the accessibility hypothesis say?
Histone variants and histone modifications directly alter the affinity between DNA and the histone octamer, changing chromatin accessibility
What is the main idea of the accessibility hypothesis in one phrase?
Histone changes act directly on chromatin structure
What Drosophila example supports the accessibility hypothesis?
H4K16ac is enriched on the male X chromosome, which is hyperactive
What effect does H4K16ac have on 30 nm fiber formation?
It inhibits 30 nm fiber formation
Why would H4K16ac increase gene expression under the accessibility hypothesis?
Because it makes chromatin less compact and more accessible
What does the histone code hypothesis say?
Histone variants and modifications act as marks read by other proteins, which then change chromatin function
What is the main idea of the histone code hypothesis in one phrase?
Histone changes act indirectly by recruiting reader proteins
What Drosophila example supports the histone code hypothesis?
H3K9 methylation marks compact chromatin in the chromocentre
What protein is recruited by H3K9 methylation?
HP1, heterochromatin protein 1
What does HP1 do?
It compacts chromatin
What is the key similarity between the accessibility hypothesis and the histone code hypothesis?
Both say histone variants and histone modifications help regulate chromatin activity and gene expression
What is the key difference between the accessibility hypothesis and the histone code hypothesis?
The accessibility hypothesis says histone changes directly change DNA-histone affinity, while the histone code hypothesis says they are marks read by other proteins
What are the 3 histone functions summarized at the end of lecture 33?
Compact DNA, block promoters, and mark chromatin regions as active or inactive
What is epigenetics?
A change in gene expression that is not due to a change in DNA sequence
How is an epigenetic change different from a genetic change?
The DNA sequence stays the same, but gene expression changes
Why is epigenetics especially important after mitosis?
Because cells must re-establish the same gene expression patterns after chromosomes were condensed and transcription was shut down
During mitosis, are genes actively being transcribed according to the lecture’s example?
No
What broad group of organisms shows epigenetic phenomena?
All eukaryotes
What is one epigenetic mechanism involving proteins bound directly to DNA?
DNA-binding proteins
What example of DNA-binding proteins was given?
MSL proteins marking the overactive X chromosome in male Drosophila
What is one epigenetic mechanism involving RNA?
DNA-binding RNAs
What example of DNA-binding RNA was given?
Xist RNA marking the inactive X chromosome in female mammals
What is one epigenetic mechanism involving histone variants?
CenH3 histones marking centromeres in euk chromosomes
What is one epigenetic mechanism involving histone modifications?
H4K16ac marking the overactive X chromosome in male Drosophila
Is DNA methylation in mammals always associated with the same effect on gene expression?
No, it can increase or decrease gene expression depending on context