Mechanisms of Gene Regulation (regulation of gene expression ALA)

Transcriptional Regulation

the means by which a cell regulates the conversion of information stored in DNA to that of RNA (regulates during chromatin remodeling and gene expression)

Post-Transcriptional regulation

mechanisms controlling the processing, location, expression, and half-life of RNA

Translational Regulation

regulation of ribosome production, assembly, and localization to ER membranes (folding and transport)

Post-Translation regulation

mechanisms that influence the folding, function, location, and half-life of proteins (protein modification and degradation)

Promoters

DNA sequences that are bind to transcription factors and it’s function is to find the beginning of a gene and recruit RNA polymerase

Basal/general transcription factor

DNA that is bound by promoters and its function is to recruit RNA polymerase to activate gene expression in all cells

Enhancers

DNA that is bound by activators and its function is to help upregulate gene expression

Silencer

DNA sequences that are bound by repressors and help down-regulate gene expression

Activator

protein that is bound by enhancers and its function is enhancer

Moderators

proteins that communicate between regulatory elements (enhancers/silencers) and the transcription initiation complex

Repressors

Protein that binds to silencers and its function is to turn down (attenuate) gene expression

The functioning of enhancers is an example of

transcriptional control of gene expression

Correct statement for an enhancer

a sequence associated with a protein to initiate transcription

How is an enhancer that is thousands of base-pairs away from a gene able to regulate transcription of a gene that is so far away?

DNA looping with the help of a mediator brings it physically close to the promoter

CACTAAAG is associated with dark hair, CGCTAAG is associated with blond. How could these nearly identical enhancer-binding sites lead to different rates of initiating transcription of the regulated gene?

the transcription factor could bind to the enhancers with different affinities, with the sequence promoting stronger binding leading to higher rates of transcription

Alternative RNA splicing

can allow the production of proteins of different sizes and functions from a single mRNA

Epigenetic

surface-level covalent modifications that can be added to histones or directly to DNA sequences that influence the state (open or closed) of chromatin and thus the accessibility of genes. DNA sequences are NOT changed even though the gene expression may be and many modifications are heritable

Histone code

chemical modifications to histone proteins on their tails

Examples of covalent histone modifications

Acetyl, Methyl, Phosphate, Ubiquitin, Sumo

DNA methylation

attachment of methyl groups to cytosines in DNA

How does DNA methylation regulate gene expression

often silences transcription; DNA methyltransferases do this and demethylases reverse; found in CpG islands; heritable

Histone methylation

covalent attachment of methyl groups to amino termini of specific histones; locations are often lysine residues

How does histone methylation regulate gene expression?

may activate or silence by blocking transcriptional regulators’ access to enhancers and promoters, but is reversible; done by methylase/demethylases; recruit chromatin remodeling complexes to promote heterochromatin formation; example is X-chromosome inactivation

Histone acetylation

covalent attachment of acetyl groups to amino termini of specific histones; locations are often lysine are arginine residues

How does histone acetylation regulate gene expression?

acetyl groups disrupt the DNA-histone (-/+) interaction to loosen/decondense chromatin to allow transcriptional regulators to identify enhancers and promoters and recruit RNA polymerase; acetylases add acetyl group, while deacetylases remove them; recruit chromatin remodeling complexes to space out or remove histones

Histone variants

replacement of standard histones with variants; examples are MacroH2A in inactivated X chromosomes, H2A.X in DNA repair, cenH3 in centromere, spH2B in telomeres of sperm cell chromosomes

How do histone variants regulate gene expression?

may silence or activate genes; signal to transcriptional regulators where to activate/inactivate expression is specific parts of the genome

Ubiquitin

Where is a Ubiquitin added onto a protein target

Function of proteasome

degrade ubiquitinated proteins

Major parts of the proteasome

regulatory particle, core particle, ATPases

Does the proteasome require an energetic input to function

Yes, ATP

Where does the breakdown of the protein occur in the proteasome

in the core particle

What happens to the broken down parts of the degraded proteins

they are recycled