Chapter 15

How are the functions of regulatory transcription factor proteins controlled?

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

What factors contribute to combinatorial control?

- one or more activator proteins - one or more repressor proteins - binding of small effector molecules - protein-protein interactions - covalent modifications - alteration of the composition or arrangement of nucleosomes - DNA methylation - formation of heterochromatin

How do most regulatory transcription factors exert their effects?

- regulation via TFIID - regulation via mediator - regulation via changes in chromatin structure

How can nucleosomes change?

- their locations can be altered along a DNA molecule by either a change in their spacing or the removal of histone octamers - histones exist in different variants that play specialized roles - histones are subject to covalent modifications at their animo-terminal tails

How do histone modifications affect the level of transcription?

- they may directly influence interactions within nucleosomes - they occur in patterns that are recognized by proteins - the pattern of histone modification acts much like a language or code in specifying alterations in chromatin structure

What has nucleosome mapping determined?

- where nucleosomes are located - where histone variants are found - where covalent modifications of histones occur

How do chromatin remodeling complexes change chromatin structure?

-change in nucleosome position - eviction of histone octamers - replacement with histone variants

Steps of transcriptional activation of a eukaryotic gene

1. Binding of activator 2. Chromatin remodeling and histone modification 3. Formation of the pre initiation complex 4. Elongation

Enhancer

A DNA sequence that recognizes certain transcription factors that can stimulate transcription of nearby genes

Silencer

A eukaryotic DNA sequence that functions to inhibit the start of gene transcription

Repressor

A protein that suppresses the transcription of a gene

DNA methylation

DNA structure can be modified by the covalent attachment of methyl groups

Open conformation

When chromatin is in a(n) ______ ______ it is more easily accessible to transcription factors and RNA polymerase, allowing transcription to occur

DNA translocase

a catalytic ATPase subunit that moves along the DNA; component of chromatin-remodeling complexes.

Transcription factor

a category of proteins that influence the ability of RNA polymerase to transcribe DNA to RNA

TFIID

a general transcription factor that binds to the TATA box and is needed to recruit RNA polymerase II to the core promoter

Nucleosome free region (NFR)

a region of DNA where nucleosomes are not found; typically 150 bp in length

Orientation-independent/bidirectional

a regulatory element can function in the forward or reverse direction

cAMP response element-binding protein (CREB protein)

a regulatory transcription factor that becomes activated in response to cell-signaling molecules that cause an increase in the cytoplasmic concentration of the molecule cyclic adenosine monophosphate (cAMP)

ATP-dependent chromatin-remodeling complexes

a set of diverse multi-protein machines that reposition and restructure nucleosomes

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

a. influences chromatin structure

The binding of iron regulatory protein (IRP) to the iron response element (IRE) in the 5' region of the ferritin mRNA results in the a. inhibition of translation of the ferritin mRNA b. stimulation of translation of the ferritin mRNA c. degradation of the ferritin mRNA d. both a and c

a. inhibition of translation of the ferritin mRNA

Histone variants

accumulated mutations that change the amino acid sequences of histone proteins; altered histones

Histone acetyltransferase

acetylate positively charges lysines within the core histone proteins

Up regulation

action of enhancers

Down regulation

action of silencers

DNA methyltransferase

attaches a methyl group to the carbon at the number 5 position of the cytosine base, forming 5-methylcytosine

A bidirectional enhancer has the following sequence: 5'-GTCA-3' 3'-CAGT-5' Which of the following sequences would also be a functional enhancer? a. 5'-ACTG-3' 3'-TGAC-5' b. 5'-TGAC-3' 3'-ACTG-5' c. 3'-GTCA-5' 5'-CAGT-3' d. 3'-TGAC-5' 5'-ACTG-3'

b. 5'-TGAC-3' 3'-ACTG-5'

A regulatory transcription factor protein typically contains ______ that binds to the _____ of the DNA. a. an a helix, backbone b. an a helix; major groove c. a B sheet, backbone d. a B sheet, major groove

b. an a helix; major groove

The process in which completely unmethylated DNA becomes methylated is called a. maintenance methylation b. de novo methylation c. primary methylation d. demethylation

b. de novo methylation

Combinatorial control refers to the phenomenon that a. transcription factors always combine with each other when regulating genes b. the combination of many 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 factors determines the expression of any given gene

Which of the following characteristics I a 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-free region c. the terminator is wrapped around a nucleosome d. none of the above characteristics is typical of a eukaryotic gene

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

The overall goal of the ENCODE Project is a. to sequence the entire genome from many different people b. to identify all of the functional elements in the human genome c. to study the expression of selected human genes d. none of the above

b. to identify all of the functional elements in the human genome

How is methylation able to alter gene expression?

because the methyl group on cytosine protrudes into the major groove of the DNA< methylation can affect the binding of proteins into that groove, and thereby affect transcription

Steroid receptor

binds directly to the protein; functions to affect gene transcription, usually by increasing the rate of transcription

Transcriptional activation of eukaryotic genes 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

How can methylation affect transcription? a. it may prevent the binding of regulatory transcription factors b. it may enhance the binding of regulatory transcription factors 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 are possible ways for methylation to affect transcription

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

d. any of the above

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

d. do all of the above

ATP-dependent chromatin remodeling/chromatin remodeling

dynamic changes in the structure of chromatin that occur during the life of a cell; the energy of ATP hydrolysis is used to drive changes in the positions and/or compositions of nucleosomes, thereby making the DNA more or less amenable for both the activation and repression of transcription

Activator

enhance the rate of transcription

Tissue-specific genes

genes that are highly regulated and may be expressed only in a particular cell type

Housekeeping genes

genes that encode proteins required in most cells of a multicellular organism

Why is the alpha helix common in transcription factors?

it is the proper width to bind into the major groove of the DNA double helix

Combinatorial control

most eukaryotic genes are regulated by many factors

Transactivation domain

promotes the activation of RNA polymerase, often by interacting with general transcription factors

Methyl-CpG-binding proteins

proteins that bind methylated sequences

Coactivators

proteins that increase the rate of transcription but do not directly bind to the DNA itself

General transcription factors

required for the binding of RNA polymerase to the core promoter to the core promoter and for progression to the elongation stage

Regulatory transcription factors

serve to regulate the rate of transcription of target genes; influence the ability of RNA polymerase to begin transcription of a particular gene

Why must the functions of regulatory transcription factors be modulated?

the genes they control must be turned on at the proper time, in the correct cell type, and under appropriate environmental conditions

De novo methylation

the methylation of DNA that was previously unmethylated

Maintenance methylation

the methylation of hemimethylated DNA following DNA replication; preserves the methylated condition in future cells; does not act on unmethylated DNA

Mediator

the observation that this complex mediates the interaction between RNA polymerase II and regulatory transcription factors

Histone code hypothesis

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

Gene regulation

the phenomenon in which the level of gene expression is controlled so that genes can be expresses at high or low levels

Major groove

the region of the DNA double helix where the nucleotide bases are in contact with the water in cellular fluid

Motif

the structurally similar region in a domain; promote protein dimerization

Heterodimer

two different transcription factors

Dimer

two identical molecules bonded together

Homodimer

two identical transcription factors

Iron regulatory protein (IRP)

two mRNA's that encode ferritin and the transferrin receptor are both influenced by an RNA-binding protein

Closed conformation

when chromatin is in a(n)_______ __________ transcription may be difficult or impossible