Chapter 17.1-17.3: Gene Regulation in Eukaryotes

Why is gene expression regulation important in eukaryotes?

It is required to respond to changing environmental conditions.

What is one reason for regulating gene expression during development in eukaryotes?

To express only those proteins needed at particular times in development.

What does gene expression regulation help define in eukaryotic cells?

It helps express only proteins that define a specific cell or tissue type.

Gene expression regulation in prokaryotes

Primarily needed for survival and efficiency.

What are general transcription factors?

Proteins required for the binding of RNA polymerase to the core promoter.

What is the role of general transcription factors in transcription?

They facilitate the progression of RNA polymerase to the elongation stage.

What do regulatory transcription factors bind to?

Control elements or regulatory elements

Where are regulatory elements mostly located?

Within 500 bp upstream of the promoter

Can regulatory elements be bidirectional?

Yes

Activator

A transcriptional regulatory protein that binds to DNA and increases the rate of transcription.

Repressor

A regulatory protein that binds to DNA and inhibits transcription.

What is an enhancer?

A DNA sequence that functions as a regulatory element.

What is the role of a regulatory transcription factor in relation to an enhancer?

The binding of a regulatory transcription factor to the enhancer increases the level of transcription.

What is a silencer in genetics?

A DNA sequence that functions as a regulatory element.

What effect does the binding of a regulatory transcription factor to a silencer have?

It decreases the level of transcription.

What are small effector molecules?

Non-protein, often metabolite-like molecules that influence gene expression.

How do small effector molecules influence gene expression?

By binding to regulatory proteins.

What effect do small effector molecules have on DNA-binding proteins?

They change the shape or activity of DNA-binding proteins.

What is combinatorial control?

The phenomenon in eukaryotes where the combination of many factors determines the expression of any given gene.

In which type of organisms does combinatorial control occur?

Eukaryotes

What is TFIID?

A general transcription factor.

What is the function of TFIID?

It recruits RNA polymerase to the promoter.

What can activate or repress TFIID?

Regulatory transcription factors.

What is a mediator in the context of transcription?

A protein complex that mediates interactions between RNA polymerase II and regulatory transcription factors.

What role does the mediator play in transcription?

It controls whether RNA polymerase II can progress to the elongation stage.

Regulatory transcription factors regulation mechanisms

Includes binding of small effector molecules (inducers, corepressors, or inhibitors), protein-protein interactions, and covalent modifications.

Steroid hormone receptors

Regulate gene expression by binding to their hormone, acting as transcription factors to regulate target genes.

How do glucocorticoids enter a cell?

Hormone diffuses through the plasma membrane.

What do glucocorticoids bind to after entering a cell?

They bind to glucocorticoid receptors.

What is released when glucocorticoids bind to their receptors?

HSP90 is released.

What is exposed after HSP90 is released from glucocorticoid receptors?

A nuclear localization signal

What happens to glucocorticoid receptors after the nuclear localization signal is exposed?

They dimerize.

Where do glucocorticoid receptors go after dimerization?

They enter the nucleus.

What do glucocorticoids bind to in the nucleus?

They bind to a glucocorticoid response element.

What is activated when glucocorticoids bind to the glucocorticoid response element?

Transcription is activated.

What is the composition of a nucleosome?

An octamer of core histone proteins (H2A, H2B, H3, H4), H1, and linker DNA.

What are the core histone proteins in a nucleosome?

H2A, H2B, H3, H4

What is the role of H1 in a nucleosome?

linker histone that helps stabilize the nucleosome structure.

What is linker DNA in the context of a nucleosome?

the stretch of DNA that connects nucleosomes.

What is chromatin remodeling?

Processes that change chromatin conformation affecting transcription levels.

What type of complexes are required for chromatin remodeling?

ATP-dependent chromatin remodeling complexes.

Name an example of an ATP-dependent chromatin remodeling complex.

SWI/SNF

Open conformation (euchromatin)

More transcription occurs in this state.

Closed conformation (heterochromatin)

Less transcription occurs in this state.

ATP-dependent chromatin remodeling complexes

Include families such as SWI/SNF, ISWI, INO80, and Mi-2, which have DNA translocases that move along DNA and reposition nucleosomes.

Nucleosome repositioning

Creates an open space without nucleosomes, changes spacing of nucleosomes, and increases accessibility.

Nucleosome composition change

Involves changing the composition of nucleosomes to affect gene expression.

What is a histone variant?

A type of histone that differs from standard histones.

How do histone variants differ from standard histones?

They differ due to duplications and mutations.

What role do histone variants play in the cell?

They play specialized roles in chromatin structure and function.

CenH3 (CENP-A)

A histone variant found at the centromere.

macroH2A

A histone variant found along the inactive X chromosome.

H3K4me3

A histone modification associated with activated gene expression, found at active promoters.

H3K9me3

A histone modification associated with repressed gene expression, marking heterochromatin.

H3K27me3

A histone modification associated with repressed gene expression, involved in polycomb-mediated silencing.

Acetylation

A histone modification that activates gene expression by promoting open chromatin structure.

What is the histone code hypothesis?

A theory proposing that histone modifications extend the information potential of the genetic code.

What does the histone code hypothesis represent?

A fundamental regulatory mechanism impacting chromatin-templated processes.

Histone methyltransferase

An enzyme that adds methyl groups to histones, serving as a writer for methylation.

Histone demethylase

An enzyme that removes methyl groups from histones, serving as an eraser for methylation.

Kinase

An enzyme that adds phosphate groups to histones, serving as a writer for phosphorylation.

Phosphatase

An enzyme that removes phosphate groups from histones, serving as an eraser for phosphorylation.

Histone acetyltransferase

An enzyme that adds acetyl groups to histones, serving as a writer for acetylation.

Histone deacetylase

An enzyme that removes acetyl groups from histones, serving as an eraser for acetylation.

Nucleosome free region (NFR)

A region around the core promoter that is approximately 150 bp long and flanked by two well-positioned nucleosomes.

DNA methyltransferase

The enzyme that attaches methyl groups to adenine or cytosine bases.

What is 5-methylcytosine (5Mc)?

A modified form of the DNA base cytosine.

What is added to cytosine to form 5-methylcytosine?

A methyl group (-CH₃) is added to the 5th carbon of the cytosine ring.

Unmethylated CpG

CpG sites that allow transcription to occur by keeping the DNA accessible.

Hemi-methylated CpG

CpG sites that are briefly methylated after DNA replication before being converted to fully methylated.

Methylated CpG

CpG sites that are fully methylated and are associated with gene silencing and chromatin compaction.

CpG islands

Clusters of CG sequences near a gene's promoter that, when methylated, usually inhibit transcription.

De novo methylation

The methylation of DNA that has not been previously methylated, usually a highly regulated event.

Maintenance methylation

The methylation of hemimethylated DNA following DNA replication.

What is the role of unmethylated CpG islands in housekeeping genes?

They regulate transcription.

What is the role of methylated CpG islands in tissue-specific genes?

They potentially block activator binding sites.

What can methylation of CpG islands promote?

Heterochromatin formation.

What happens to DNA methylation patterns during cell division?

Methylated DNA sequences are inherited.

What can cause specific genes to be methylated?

Development or response to the environment.