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Gene regulation in eukaryotes I: Transcriptional and translational regulation - Chromatin remodeling, histone variants, and histone modifications

28 important questions on Gene regulation in eukaryotes I: Transcriptional and translational regulation - Chromatin remodeling, histone variants, and histone modifications

What is ATP-dependent chromatin remodeling or chromatin remodeling?

Dynamic changes in the structure of chromatin that occur during the life of a cell.

What is responsible for changing the structure of chromatin?

ATP-dependent chromatin-remodeling complexes, which are a set of multi-protein machines.

Is chromatin remodeling important for activation or repressing of transcription?

For both.

How is the catalytic ATPase subunit of chromatin-remodeling complexes called?

DNA translocase-

Why is it called SWI/SNF-family?

The SWI and SNF refer to the effects that occur when these complexes are inactive. SWI mutants are defective in mating-type switching, and SNF mutations create a sucrose nonfermenting phenotype.

What are the 3 possible effects of chromatin remodeling?

- A change in the positions of nucleosomes;
- Removing histone octamers, creating gaps;
- Removing standard histones and replacing them with histone variants.
(Fig. 15.9 on p. 379).

What are histone variants?

A few histone genes have mutations in them, which express different histones, called histone variants.

What is the function of those histone variants?

Regulating the structure of chromatin, thereby influencing gene transcription.

Do histone variants activate or repress gene expression?

It depends on the variant, some activate gene expression and others repress.

What other kinds of functions could histone variants have?

For example, the binding of kinetochore proteins or DNA repair.

What do the core histone proteins consist of?

A globular domain and an amino-terminal tail.

Why do histone proteins easily interact with the DNA backbone?

Because histone proteins are usually positively charged (due to the positively charged amino-terminal tail) and the DNA backbone is negatively charged.

By what type of enzyme are positively charged lysines in the amino-terminal tail acetylated?

By histone acetyltransferase.

What happens when lysine is acetylated?

The positive charge of lysine is eliminated, and the electrostatic attraction between the histone protein and the DNA backbone is disrupted.

What is the histone code hypthesis?

A hypothesis proposed by Strahl, Allis, and Turner in 2000. According to this hypothesis, the pattern of histone modifications (for example phosphorylation on certain positions) acts as a language or code.

What can such a pattern of covalent modifications subsequently affect?

The degree of transcription.

How is a pattern of histone modifications able to affect the degree of transcription?

A pattern of modifications could attract proteins that inhibit transcription, and a different combination could attract proteins that alter the positions of nucleosomes in a way that promotes gene transcription.

In conclusion, in which two ways can histone modifications affect the level of transcription?

- Modifications could lead to disruption of the attraction between the histone protein and the DNA backbone, which could promote transcription.
- Modifications could lead to the binding of certain proteins that inhibit or promote gene transcription.

Researchers have been able to map the locations of specific nucleosomes and histone variants within the genome. How is the approach they used called?

Chromatin immunoprecipitation sequencing (ChIP-Seq).

What do studies using ChIP-Seq show?

That many eukaryotic genes show a common pattern of nucleosome organization.

How is the region called where the transcriptional start site at the core promoter is found in active genes or genes that can be activated?

A nucleosome free region (NFR), a region in DNA where nucleosomes are not found.

How are the nucleosomes at the end of a gene positioned?

They are well-positioned, followed by an NFR.

What do certain transcriptional activators recruit?

Chromatin-remodeling complexes and histone-modifying enzymes to the promoter region.

What is the order in which the proteins of gene regulation may act at the promoter region, to promote transcription?

An activator binds to an enhancer in the NFR. The activator recruits a chromatin-remodeling complex and a histone-modifying enzyme to this region. The latter protein can remove or shift nucleosomes. These actions facilitate the binding of general transcription factors and RNA polymerase

What must be altered in the nucleosome organization for transcription to occur?

Histone octamers have to be evicted or destabilized.

What are the evicted histone proteins transferred to?

Histone chaperones.

What do histone-modifying enzymes do during elongation?

They travel with RNA polymerase II and modificate histone proteins.

After RNA polymerase has transcribed a part of the DNA, what happens to the nucleosome organization?

It turns back to normal to maintain the fidelity of transcription of the following DNA.

The question on the page originate from the summary of the following study material:

Genetics: Analysis & Principles II

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