Gene regulation in eukaryotes: transcriptional regulation

The functions of regulatory transcription factor proteins are controlled in three common ways: through

(1) the binding of a small effector molecule; small effector molecule may bind to a regulatory transcription factor and promote its binding to DNA (2) protein-protein interactions; formation of homodimers and heterodimers is a fairly common means of controlling transcription. (3) covalent modifications; function of a regulatory transcription factor can be affected by covalent modifications, such as the attachment of a phosphate group

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 change the structure of chromatin in a way that inhibits transcription.

Repressor

A regulatory transcription factor that acts as this, that inhibits the rate of transcription by binding to its regulatory element, a silencer

Mediator

A second way regulatory transcription factors control RNA polymerase II is does protein complex; refers to the observation that it mediates the interaction between RNA polymerase II and regulatory transcription factors; it controls the ability of RNA polymerase II to progress to the elongation stage of transcription via phosphorylation of the carboxyl-terminal domain.

Enhancer

A sequence that a regulatory transcription factor binds to called a regulatory element

Activator

A transcription factor that enhances the rate of transcription; binds to a regulatory element called an enhancer

Steroid receptor

A type of regulatory transcription factor; steroid hormone binds directly to the protein

NOTE*

Another interesting feature in certain motifs is they promote dimerization

Up Regulation

Enhancers can stimulate transcription 10- to 1000-fold, a phenomenon known as...

Bidirectional

Many regulatory elements are orientation independent; aka...?

α helix

Secondary structure; is frequently found in transcription factors; the α helix is the proper width to bind into the major groove of the DNA double helix.

NOTE*

Some regulatory transcription factors bind to a regulatory element and then influence the function of TFIID.

Domains

Transcription factor proteins contain regions that have specific functions; One domain may have a DNA-binding region and another domain may be for binding effector molecule

Repressors (Mediators)

activator binds to a distant enhancer element; activator protein and mediator are brought together by the formation of a loop within the intervening DNA; alternatively, "blank" protein may prevent mediator from allowing RNA polymerase to proceed to the elongation phase of transcription

Zinc finger motif

composed of one α helix and two β-sheet structures that are held together by a zinc (Zn 2) metal ion

Activator proteins TFIID

expected to enhance the ability of TFIID to initiate transcription; could help TFIID bind to the TATA box or they could enhance the function of TFIID in a way that facilitates its ability to recruit RNA polymerase II; sometimes exert their effects by interacting with co activators

Repressor proteins TFIID

inhibit the function of TFIID; exert their effects by preventing the binding of TFIID to the TATA box; or by inhibiting the ability of TFIID to recruit RNA polymerase II to the core promoter.

TFIID

is a general transcription factor that binds to the TATA box and is needed to recruit RNA polymerase II to the core promoter; activator proteins are expected to enhance the ability of this

Coactivators

proteins that increase the rate of transcription but do not directly bind to the DNA itself; typically contain a trans activation domain that promotes the activation of RNA polymerase, often by interacting with general transcription factors.

NOTE*

recognition helix often contains many positively charged amino acids (e.g., arginine and lysine) that favorably interact with the DNA backbone, which is negatively charged.

Gene regulation

refers to the phenomenon that the level of gene expression can be controlled so that genes can be expressed at high or low levels.

Major groove

region of the DNA double helix where the bases contact the surrounding water in the cell.

Transcription factor

to describe proteins that influence the ability of RNA polymerase to transcribe a given gene.

NOTE*

Hydrogen bonding between the amino acid side chains in an α helix and nucleotide bases in the DNA is one way that a transcription factor binds to a specific DNA sequence.

Helix turn and helix loop

In these, α helix called the recognition helix makes contact with and recognizes a base sequence along the major groove of the DNA

Regulatory transcription factors and regulatory elements

When bound they affect the transcription of an associated Gene

TF's that affect RNA polymerase ability to begin transcription

regulate the binding of the transcriptional complex to the core promoter and/or control the switch from the initiation to the elongation stage of transcription.

Down Regulation

regulatory elements that serve to inhibit transcription are called silencers, and their action is called...

General transcription factors

required for the binding of RNA polymerase to the core promoter and its progression to the elongation stage; necessary for any transcription to occur

Regulatory transcription factors

serve to regulate the rate of transcription of target genes; exert their effects by influencing the ability of RNA polymerase to begin transcription of a particular gene.

combinatorial control

Most eukaryotic genes found in multicellular species are regulated by many factors; the combination of many factors determines the expression of any given gene.

Transcriptional activators (Mediators)

stimulate the ability of mediator to cause the phosphorylation of the carboxyl-terminal domain, thereby facilitating the switch between the initiation and elongation

NOTE*

that regulatory transcription factors influence transcription is by recruiting proteins to the promoter region that affect nucleosome positions and compositions; ex, certain transcriptional activators recruit proteins to the promoter region that alter chromatin structure.

Heterodimer

Two different transcription factors come together inform this

Homodimer

Two identical transcription factor proteins may come together to form this

Motif

When a domain or portion of a domain has a similar structure in many different proteins