BIOL 4003 : Module 8

Common factors contributing to combinatorial control

1. 1+ activator proteins may stimulate transcription 2. 1+ repressor proteins may inhibit transcription 3. Activators and repressors may be modulated by - small effector molecules - protein-protein interactions - covalent modifications 4. Regulatory proteins may alter nucleosomes (composition or location) near the promoter 5. DNA methylation may inhibit transcription - Prevent binding of an activator protein 6. The formation of heterochromatin may inhibit gene expression in localized regions

Examples of specific functions domains may have

1. DNA-binding 2. Binding site for small effector molecules 3. Dimerization

What are the 2 main types of transcription factors?

1. General transcription factors : required for the binding of RNA polymerase to the core promoter and its progression to the elongation stage - Always required - Necessary for basal transcription 2. Regulatory transcritption factors : Serve to regulate the rate of transcription of target genes - typically, influence the ability of RNA polymerase to begin transcription of a particular gene - Most common : regulate initiation phase (although there are others that regulate other phases as well)

DNA methylation may inhibit transcription through which two outcomes?

1. prevent binding of an activator protein 2. recruiting proteins that compact the chromatin --> Inhibits RNA polymerase II and general transcription factors from accessing the promoter

A bidirectional enhancer has the sequence 5'-GTCA-3' and 3'-CAGT-5' what would be a functional enhancer?

5'-TGAC-3' and 3'-ACTG-5'

The binding of a transcription to an enhancer ____________ rate of transcription? A. Decreases B. Increases C. None of the above

A : Increases

What is a motif?

A domain, or a portion of a domain that has a very similar structure in many different proteins i.e. : DNA-binding motif or a dimerization motif

Repressors binds to what?

A silencer

Gene activation diagram

Activator + enhancer Binding of an activator to an enhancer facilities the assembly of GTFs and RNA polymerase at the core promoter

Activator protein binds to what?

An enhancer

A regulatory transcription factor protein typically contains _________ that binds to the ________ of the DNA A. an alpha helix, backbone B. an alpha helix, major groove C. a beta sheet, backbone D. a beta sheet, major groove

B : An alpha helix, major groove

Regulatory transcription factors recognize ___ regulatory elements that are typically located near the core promoter. What three elements are known as these sequences?

Cis 1. Control elements 2. Regulatory elements 3. or Regulatory sequences --> All mean the same thing

The binding of a transcription factor to a silencer ________ rate of transcription and is _________ related to factor + enhancer.

Decreases Inversely related : down-regulation

Structural features of regulatory transcription factors transcription factor proteins contain regions, called _______ that have specific functions

Domain

T /F : Nerve and Muscles cells appear different due to varying DNA content

False : different gene regulation Note : some gene expression does overlap between the two types

Many response elements of enhancers and silencers can function in which directions?

Forward or reverse orientation 5'-GATA-3' or 5'-TATC-3' 3'-CTAT-5' or 3'-ATAG-5' --> this would result if you were standing on your head. Transcription factors could bind to the one on the right or the one on the left But if you rotated the left 180 degrees.... you would have the same thing as the one on the right

Combinatorial control

Genes that are regulated by many factors

Up-regulation of transcription factor bind with enhancer is quite ______ and is about....

Large ; 10-fold to 1,000-fold

How does a Leucine zipper form? What results? Leucine zipper motif structure and process

Leucine residues of side chains "zip up" and cause protein subunits to dimerize.

Activator

Regulatory protein that increases the rate of transcription

Gene repression diagram

Repressor + silencer Binding of a repressor to a silencer inhibits the assembly of GTPs and RNA polymerase at the core promoter

Eukaryotic genes are regulated by how many factors?

Several!!

Repressors bind with what types of sequences?

Silencer

In bacteria, how many transcription factors regulate genes?

Sometimes : more than 1 - Not as common in comparison to eukaryotic gene regulation

The binding of regulatory transcription factors to control elements affects what?

The transcription of an associated gene

T / F : Many response elements are orientation independent or bidirectional

True

T / F : Transcription factors are proteins that influence RNA polymerase to transcribe a given gene

True

T /F : In order for a gene to be activated, the activator must bind with an enhancer and results in the assembly of GTFs and RNA polymerase at the core promoter

True

T/F : Variation in gene expression at different stages of development resuls in some genes to be expressed during embryonic stages of developement

True

T / F : Distinct cell types require different types of gene expression

True : nerve and muscles look different due to different gene regulation rather

Most response elements are located within a a few hundred nucleotides ______ of the ______

Upstream Promoter

In regard to the contributing factors to combinatorial control, how many of these do genes experience?

Various combinations of these factors can contribute to the regulation of a single gene --> Most complex eukaryotic cells or genes experience a variety of these combinations

According to the histone code hypothesis, the pattern of histone modification acts like a language that : a. influences chromatin structure b. promotes transcriptional termination c. inhibits the elongation of RNA polymerase d. all of the above

a : influences chromatin structure

Which of the following charactersitics is typical of a eukaryotic gene that can be transcribed? a. the core promoter is wrapped around a nucleosome b. the core promoter is found in a nucleosome-freeregion c. the terminator is wrapped around a nucleosome d. none of the above

b : the core promoter is found in a nucleosome-free region

Combinatorial control refers to the phenomenon that : a. transcription factors always combine with each other when regulating genes b. the combination of many transcription factors determines the expression of any given gene c. Small effector molecules and regulatory transcription factors are found in many different combinations d. Genes and regulatory transcription factors must combine with each other during gene regulation

b. the combination of many transcription factors determines the expression of any given gene

A chromatin-remodeling complex may : a. change the locations of nucleosomes b. evict histones from DNA c. replace standard histones with histone variants d. all of the above

d : all of the above

How can methylation affect transcription? a. may prevent the binding of regulatory transcription factors b. it may enhance the binding of regulatory transcription c. it may promote the binding of methyl-CpG-binding proteins which inhibit transcription, to a methylated sequence d. all of the above are possible ways for methylation to affect transcription

d : all of the above

Regulatory transcription factors can be modulated by a. bind of small effector molecules b. protein-protein interactions c. covalent modifications d. all of the above

d : all of the above

Transcriptional activation of eukaryotic gene involves which of the following events? a. changes in nucleosome locations b. changes in histone composition within nucleosomes c. histone modifications d. all of the above

d : all of the above

Most general transcription factors bind to which location on DNA?

major groove

What is the regulatory sequence that decreases the rate of transcription?

repressor

what sequence does the activator bind to?

the enhancer