Genetics ch.17

Mediator

A protein complex that interacts with RNA polymerase II and various regulatory transcription factors. Depending on its interactions with regulatory transcription factors, mediator may stimulate or inhibit RNA polymerase II.

coactivators

A protein that does not bind directly to the DNA, but plays a role in the activation of transcription.

down regulation

genetic regulation that leads to a decrease in gene expression.

Describe how chromatin-remodeling complexes alter nucleosomes.

-One result of ATP-dependent chromatin remodeling is a change in the positions of nucleosomes. This may involve shifts in nucleosomes to new locations or changes in the relative spacing of nucleosomes over a long stretch of DNA. - A second effect is that remodelers may evict histones from the DNA, thereby creating gaps where nucleosomes are not found. -A third possibility is that remodelers may change the composition of nucleosomes by removing standard histones and replacing them with histone variants.

Regulatory transcription factors can be modulated by

-the binding of small effector molecules -protein-protein interactions -covalent modifications

Explain how histones modifications affect transcription.

-they may directly influence interactions between histones and the DNA. -histone modifications occur in patterns that are recognized by proteins. - The pattern of covalent modifications to the amino to the amino-terminal tails provides binding sites fpr proteins that subsequently affect the degree of transcription.

Summarize the steps that occur for transcriptional activation of a eukaryotic gene.

1. A transcriptional activator binds to an enhancer in thhe NFR. 2. The activator then recruits chromatin-remodeling complexes and histone-modifying enzymes to this region. The chromatin remodelers may shift nucleosomes or temporarily evict nucleosomes from the promoter region. 3. The actions of chromatin-remodeling complexes and histone-modifying enzymes facilitate the binding of general transcription factors and RNA polymerase II to the core promoter, thereby allowing the formation of a preinitiation complex. 4. For elongation to occur, histones are evicted, partially displaced, or distabilized so that RNA polymerase II can move along the DNA. Evicted histones are transferred to histone chaperones, which are proteins that bind histones and aid in the assembly of histones. Assembled histones are then placed back on the DNA behind the moving RNA polymerase II.

List the factors that contribute to combinatorial control

1. One or more activator proteins may stimulate the ability of RNA polymerase to initiate transcription. 2. One or more repressor proteins may inhibit the ability of RNA polymerase to initiate transcription. 3. The function of activators and repressors may be modulated in a variety of ways, including the binding of small effector molecules, protein-protein interactions, and covalent modifications. 4. Regulatory proteins may alter the composition or arrangements of nucleosomes in the vicinity of a promoter, thereby affecting transcription. 5. DNA methylation may inhibit transcription, either by preventing the binding of an activator protein or by recruiting proteins that cause the chromatin to become more compact.

Describe three ways that the function of a regulatory transcription factor can be modulated.

1. The binding of small effector molecules 2. protein-protein interactions 3. Covalent modifications

Outline the steps whereby glucocorticoid receptors regulate genes.

1. The hormone enters the cytosol of a cell by diffusing through the plasma membrane. 2. Once inside, the hormone specifically binds to a glucocorticoid receptor. Note: Prior to hormone binding, the glucocoticoid receptor is complexed with proteins known as heat shock proteins (HSP), one example HSP90. 3. After the hormone binds to the glucocorticoid receptor, HSP90 is released, therebty expsoing a nuclear localization signal (NLS) that directs the receptor protein into the nucleus. 4. Two glucocorticoid receptors form a homodimer and then travel through a nuclear pore into the nucleus. 5. In the nucleus, the glucocorticoid receptor homodimer binds to a glucocorticoid response elemet (GRE) with two copies of the following consensus sequence: 5'-AGRACA-3' / 3'-TCYTGT-5' where R is a purine and Y is a pyrimidine. A GRE is found next to many genes and functions as an enhancer. 6. The binding of glucocorticoid receptor homodimer to a GRE activates the transcription of the nearby gene, eventually leading to the synthesis of the encoded protein.

enhancer

A DNA sequence that functions as a regulatory element. The binding of a regulatory transcription factor to the enhancer increases the level of transcription.

Silencer

A DNA sequence that functions as a regulatory element. This binding of a regulatory transcription factor to the silencer decreases the level of transcription.

transcription factors

A broad category of proteins that influence the ability of RNA polymerase to transcribe DNA into RNA.

Chromatin remodeling

A change in chromatin structure that alters the composition of histones or the spacing of nucleosomes (or both).

regulatory sequence (regulatory element or control element)

A sequence of DNA (or possibly RNA) that binds a regulatory protein and thereby influences gene expression. Bacterial operator sites and eukaryotic enhancers and silencers are examples.

TFIID

A type of general transcription factor in eukaryotes that is required for the function of RNA polymerase II. It binds to the TATA box.

DNA translocase

A type of motor protein that can move along DNA or cause DNA to move.

histone acetyltransferase

An enzyme that attaches acetyl groups to the amino-terminal ends of histone proteins.

Distinguish between general and regulatory transcription factors.

General transcription factors are essential for any transcription for all genes while regulatory transcription factors regulate transcription of specific genes. General transcription factors only regulate the housekeeping genes while regulatory transcription factors control all of the other genes.

Define histone variant, and explain why histone variants are functionally important.

Histone variants: histones that have amino acid sequence slightly different from those of the core histones and play specialized roles in chromatin structure and function. In eukaryotes histone variants are incorporated into a subset of nucleosomes to create functionally specialized regions of chromatin.

general transcription factor (GTF)

One of several proteins that are necessary for basal transcription at the core promoter in eukaryotes.

Combinatorial control refers to the phenomenon that

The combination of several factors determines the expression of any given gene.

histone code hypothesis

The hypothesis that the pattern of histone modification acts much like a language or code in specifying alterations in chromatin structure.

Explain how a regulatory transcription factor exerts its effects via TFIID or mediator.

Transcriptional activation via TFIID: Some activators stimulate the function of TFIID, thereby enhancing transcription. The activator/coactivator complex recrits TFIID to the core promoter and/or activates its function. Transcription will be enhanced. Transcriptional repression via TFIID: Regulatory transcription factors may also function as repressor. The repressor protein inhibits the binding of TFIID to the core promoter or inhibits its function. Transcription is silenced.

regulatory transcription factor

a protein or protein complex that binds to a regulatory element and influences the rate of transcription via RNA polymerase.

activator

a transcriptional regulatory protein that increases the rate of transcription.

up regulation

genetic regulation that leads to an increase in gene expression.

bidirectional

in gene regulation, refers to the ability of regulatory elements to function in either direction.

orientation-independent

refers to certain types of genetic regulatory elements that can function in the forward or reverse direction. Certain enhancers are orientation-independent.

combinatorial control

the phenomenon common in eukaryotes in which the combination of many factors determines the expression of any given gene.