Chromatin and Molecular Mechanisms of Transcription Repression and Activation Flashcards
There are positions within genomes where large heterochromatin blocks are built called _______. Genes that are close to or within these areas are strongly repressed.
Silencers
The repression of genes by silencers depends on their ________, depending on whether they are close to or within heterochromatin. This does not depend their promoters.
Position
List two examples of positional repression from the model organism S. cerevisiae?
- Mating type loci
- Sub-telomeric genes
Describe main points surrounding the mating type loci in yeast, HML and HMR.
- HML and HMR are constantly repressed.
- Genetic studies have showed several proteins that regulate this repression.
- Rap1 binds next to the repressed loci and recruits Sir proteins
- Sir proteins (Silent Information Region) proteins spread over the repressed locus
- Sir is a histone DEACETYLATES the histones at HML and HMR
- The deacetylated histones bind tighter to DNA, form heterochromatin and prevent the association of transcriptional activators to the promotors
- Histone hypo-acetylation is necessary for gene repression
Sir2 is a histone deacetyase. What does this mean?
It deacetylates the histones at HML and HMR.
Describe positional repression at the telomeres.
- Rap1 and Sir proteins bind to the telomeres.
- Sir proteins spread in the sub-telomeric regions of the chromosomes.
- Many telomeres cluster at the periphery of the nucleus and are covered with condensed hypoacetylated nucleosomes
Describe the mutational analysis conducted on histones: Lysine –> Arginine
- These mutants MAINTAIN gene repression at telomeres.
- Arg retains the positive charge, can not be acetylated to lose its positive charge
- The DNA-histone interaction is strong, chromatin is compact
- Gene repression cannot be reversed by acetylating the histones
Describe the mutational analysis conducted on histones: Lysine –> Glutamine
- These mutations ABOLISH repression at the telomeres
- Glutamine has a neutral charge (resembling acetylated Lysine)
- Glutamine cannot be deacetylated to gain a positive charge
- Chromatin is decondesnsed
- Gene cannot be repressed
Does the Lysine –> Glutamine mutation abolish or maintain gene repression at the telomeres?
Abolish -> Can not be deacetylated to gain a positive charge
Does the Lysine –> Arginine mutation abolish or maintain gene repression at the telomeres?
Maintains- Arginine retains the positive charge
In the case of positional repression, describe the role of Rap1, th telomere, Sir3/Sir 4, and Sir 2.
Rap1 - The repressor.
The telomere - The “Silencer”
Sir 3/Sir 4 - Co-repressors
Sir 2 - Histone-Deacetylase
The Sir2/3/4 complex binds Rap 1 and then spreads away from the telomere.
In the case of promoter-dependent repression and activation, ______ and ______ bind to promoters and enhancers and recruit the co-repressors or co-activators.
Repressors and activators (THESE DO NOT SPREAD)
In the case of promoter-dependent repression and activation, is the position of the gene a critical factor?
No.
Describe Ume6 and Sin3/Rpd3.
Ume6- Transcription repressor
Sin3/Rpd3 - Complex is a co-repressor
Rpd3- Histone deactylase
Transcriptional repressors often ______ interact with a histone deactylase.
Directly
Transcriptional repressors often ______ interact with a histone acetyl-transferase.
Indirectly
Describe Gcn4, SAGA and Gcn5.
Gcn4 - Transcription activator
SAGA - Complex co-activator
Gcnc5 - Histone acetyl-transferase
Ayceylated histones can recruit more co-activators via _______.
Bromo-domains
Transcriptional activators de-condense chromatin via 1. ________ and 2. ___________.
- Histone acetylation
- Chromatin remodelling
What are the two types of co-activators brought in by transcriptional activators?
- Histon acetyl-transferases
- Chromatin-remodelling complexes
All chromatin remodelling complexes are homologous to the yeast ________ complex
SWI/SNF
Once histones are acetylated, nucleosomes- DNA interaction become _________.
Loose
What do chromatin-remodelling complexes use to push nucleosomes along DNA to “open” promoters?
ATP (energy source)
How do SWI/SNF ATPases function?
They move nucleosomes along the DNA by sliding or transferring them. They shift nucleosomes away from the promoter/enhancer sites and gives transcription factors access to the DNA.
