Cell Biology Chapter 8 Notes

Chapter 8 covers the control of gene expression

Gene expression:

The process by which a gene makes a product that is useful to the cell or organism by directing the synthesis of a protein or an RNA molecule with a characteristic activity

What dictates which genes are express, how much, where, and when?

Regulatory mechanisms

When are genes expressed?

Some are expressed all the time, some for a short time, and others are expressed during different stages of life

How many genes are being expressed at any given time?

Of our 20,000 genes, a few thousand are being expressed at a time

Cell differentiation:

A process where most cell become specialized in structure, composition, and function

What is cell differentiation a result of?

Differential gene expression

What are the only cells that express the gene for Hb?

Red blood cells

Negative gene expression control:

Regulation turns off or decreases gene activity (product)

What is in charge of negative gene expression control?

Repressor proteins

Positive gene expression control?

Regulation turns on or increases gene activity (product)

What is in charge of positive gene expression control?

Activator proteins

Where are the control points for gene expression regulation?

There is a potential control point at each step of the entire process of gene expression

What are the steps of gene expression?

• Pre-transcriptional and transcriptional control (1)

• Post-transcriptional control (2,3, and 4)

• Pre-translational and translation control (5)

• Post-translational control (6 and 7)

What occurs during pre-transcriptional and transcriptional control?

Controlling when and how often a given gene is transcribed

What occurs during post-transcriptional control?

Controlling how an RNA transcript is spliced or processed (will effect RNA stability and pre-translational control), and selecting which RNAs are exported from the nucleus

What occurs during pre-translational and translational control?

Regulating how quickly certain RNAs are degraded, and selecting which mRNAs will be translated into protein and how often a given mRNA is translated

What occurs during the post-translational control?

Regulating how quickly certain proteins are degraded, and controlling how a polypeptide is processed/activated

How can pre-transcriptional control occur at the DNA level of regulation?

By changes in chromosome and DNA structure via regulatory proteins and chemical modifications

What type of packaged DNA can be formed in promoter regions?

Nucleosomes

Why are genes located in densely condensed chromosome regions (heterochromatin) usually not expressed?

Transcription proteins cannot reach the DNA

How do activator proteins work?

They recruit the chromatin-remodeling complexes to change the structure of the nucleosome allowing access for transcription factors and RNA polymerase

How do histone-modifying enzymes alter the chromatin?

Histone acetyltransferases (HATs) add acetyl groups (CH3CO) to the tails of histones (called acetylation).

What is the result of histone-modifying enzymes altering the chromatin?

Results in “loosening” up the chromatin structure, freeing up activation/promoter sites, also helps binding to the promoter of certain transcription factors that have a liking for acetyl groups

Which histone-modifying enzyme results in histones becoming more compacted?

Histone deacetylases

What do histone methyltransferases do?

Add/remove methyl groups to histone tails; can either increase or decrease transcription of genes

What effect does DNA methyltransferases have by methylating nucleotides?

Can repress transcription since methyl groups act as a blockade, preventing transcription factors and RNA polymerase the ability to bind to DNA nucleotides of the promoter

What level of control is the most regulated level?

The initiation stage of transcription

What are transcription factors?

DNA binding proteins that bind to specific regions of the DNA to influence transcription, involved in recruiting RNA polymerase to the promoter and initiating transcription

Regulatory DNA sequences:

Recognized by different specific transcription regulator proteins (factors) that are involved in repressing or activating transcription

Silencers:

Specific DNA sites (nucleotide sequences) that are binding sites for transcriptional repressors

Enhancers:

Specific DNA sites that are binding sties for transcriptional activators

Regarding RNA polymerase, what occurs in the absence of any regulatory proteins?

Some gene promoters allow RNA polymerase to weakly bind and initiate transcription

What do the domains of transcription regulators bind?

One domain is able to bind to a DNA-binding site, while another domain is involved in binding with other regulators or RNA polymerase

What are the factors that can influence the basal level of transcription of a gene?

• DNA accessibility

• Presence of certain DNA sequences (like a promoter)

• Activity of general transcription factors

How do transcriptional repressor proteins block the basal level of expression of a gene?

They bind to the DNA to block RNA polymerase from binding to the promoter

How can transcriptional activator proteins help to activate transcription?

Bind to the DNA and hep/enhance RNA polymerase binding to the promoter (called recruitment)

How can some activators and repressors exert their “effects” from a distance away from the promoter?

Binding of the activator/repressor to its regulatory site causes the DNA between that location and the promoter to loop out and bend, bringing the two sites into close proximity with one another

How do activators work?

By an indirect mechanism, such as recruiting chromatin-remodeling complexes and other factors 

Combinatorial control:

refers to the process by which groups of transcription regulators work together to determine the expression of a single gene

Alternative splicing:

Allows different forms of a protein, encoded by the same gene, to be made in different locations

What is the lifespan of an RNA molecule?

Rangers from seconds to days (or  even weeks)

How is mRNA regulated by phosphorylation?

When the binding proteins are phosphorylated, they are unable to bind to the cap binding proteins and the mRNA bind to the cap binding proteins.

How are translation initiation factors regulated by phosphorylation?

It inhibits their activation/function and results in the initiator tRNA not being able to enter the P site

What is the translation of mRNA regulated by?

Translation initiation factors that bind to specific sequences or structures of the mRNA

Translation repressor proteins:

A type of translation factor that can block the translation of mRNA; they prevent the attachment of ribosomes binding to specific nucleotide sequences in the 5’ untranslated region

On average, how long do proteins last?

1-2 days

Protease:

Enzymes that degrade proteins by a process known as proteolysis (involves hydrolyzing the peptide bonds)

Proteosomes:

Large protein machines/complexes found in the cytosol and nucleus that have a protease component

Ubiquitin:

A unique protein that marks other proteins for destruction