Genetics 15

Regulatory transcription factors

-regulate the rate of transcription of target genes -influence ability of RNA pol to being transcription of a particular gene

General transcription factors

-required for binding RNA pol to core promoter and elongation stage -needed 4 basal transcription

Gene Regulation In Eukaryotes I: What are benefits of regulating genes?

-respond to changes in nutrient availability -respond to enviormental stress

Three common interactions that communicate the effects of regulatory transcription factors are

1.TFIID-direct or through coactivators 2.Mediator 3.recruiting proteins that affect nucleosome composition

Chromatin remodeling and histone modification

An activator protein recruits a chromatin remodeling complex (such as SWI/SNF) and a histone-modification enzyme (such as histone acetyltransferase).

Iron response elements (IREs) can be found in the 5'-UTR of -----mRNA and in the 3'-UTR of------ ------ mRNA.

Blank 1: ferritin Blank 2: transferrin Blank 3: receptor

What effect can ATP-dependent chromatin remodeling have on transcription?

Both activation and repression

Select ways that nucleosomes can change.

Change in histones to variants with specialized roles Change in location Covalent modifications to the amino-terminal tails of histones

A protein that increases the rate of transcription but does not directly bind to the DNA is called a

Coactivator

Elongation:

During elongation, histones ahead of the open complex are covalently modified by acetylation and evicted. Behind the open complex, histones are deacetylated and become tightly bound to the DNA.

through ATP-dependent chromatin remodeling.

Energy of ATP hydrolysis is used to drive change in location and/or composition of nucleosomes Makes the DNA more or less amenable to transcription

Formation of the preinitiation complex:

General transcription factors and RNA polymerase II are able to bind to the core promoter and form a preinitiation complex.

Coactivators (activation of Transcription)

Large multiprotein complex =>Does not bind directly to DNA =>Activates transcription by interacting with both activator and transcription factors: Recruits coactivator and then it recruits RNA Pol II to correct position

The protein complex that mediates the interaction between RNA polymerase II and regulatory transcription factors is called

Mediators

Structure RTscriptsFs : domains

Region on a transcription factor: •could be for DNA-binding •Another could provide a binding site for effector molecules

Repressor

Regulatory transcription factor (decrease rate of tscript) sequence it binds is called an silencer

Activator

Regulatory transcription factor (increase rate of tscript) sequence it binds is called an enhancer

control elements, regulatory elements or regulatory sequences

Regulatory transcription factors recognize cis regulatory elements located near the core promoter

steroid receptors

Regulatory transcription factors that respond to steroid hormones -hormone actually binds to the TF

down-regulation

The binding of a transcription factor to a silencer decreases the rate of transcription

True or false: A transcription factor can have multiple domains.

True

DNA methylation / DNA methyltransferase

a change in chromatin structure that silences gene expression

Transcription factors

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

Insulators

are segments of DNA that insulate a gene from the regulatory effects of other genes •Some act as barriers to chromatin remodeling •Others block the effects of enhancers - •May do this by chromosome looping

The function of TFIID is to ______.

bind to the TATA box and recruit RNA polymerase II to the core promoter

up-regulation

binding of a transcription factor to an enhancer increases the rate of transcription •10- to 1,000-fold

CREB is an acronym for

cAMP response element-binding

•In tissue-specific genes: Methyl-CpG-binding proteins may recruit factors that lead to

compaction of the chromatin

GRE (Glucocorticoid Response Elements) function as

enhancers located near dozens of different genes, so the hormone can activate many genes

If chromatin is in a closed conformation, nucleosome position and histone composition ______.

make it difficult for transcription factors to gain access to and bind their target sequences in the promoter DNA

2-7% of DNA is methylated in

mammals

CpG islands near the promoters of tissue-specific genes are often ______.

methylated

2-3% of human genes encode

transcription factors

histone variants

•A few of these genes have accumulated mutations that alters the amino acid sequence Some histone variants are incorporated into a subset of nucleosomes to create specialized chromatin

Eukaryotes have multiple families of chromatin remodelers

•SWI/SNF •ISWI •INO80 •Mi-2

Click and drag on elements in order. Place these steps in a simplified model for transcriptional activation of a eukaryotic gene in order from first to last, putting the first step at the top.

1. Binding of an activator to an enhancer in the NFR2. Recruitment of a chromatin-remodeling complex and a histone-modifying enzyme3. Recruitment of general transcription factors and RNA Pol II to the core promoter, allowing the formation of a preinitiation complex4. Eviction or destabilization of histone octamers, allowing RNA pol II to pass, and elongation to occur

Never and muscle cells look so different because of

gene regulation rather than differences in DNA content

CREB protein becomes activated in response to cell-signaling molecules that cause an

increase in the cytoplasmic concentration of cAMP •Cyclic adenosine monophosphate

Many response elements (enhancers and silencers?) are

orientation independent or bidirectional -upstream of he promoter (usually)

How may DNA methylation inhibit transcription?

•prevent binding of an activator protein •recruiting proteins that compact the chromatin

Activity of the CREB Protein

cAMP Acts as a second messenger •Activates protein kinase A -Phosphorylated CREB binds to DNA and stimulates transcription Unphosphorylated CREB can bind to DNA, but cannot activate RNA pol

Nucleosomes can

change in location along a DNA molecule, by replacement of a standard histone with a histone variant, and through covalent modifications on histone tails.

Structure of RTscriptF's : motif

is a domain, or a portion of a domain, that has a very similar structure in many different proteins

CpG Islands

near promoters 1,000 to 2,000 nucleotides long

Transcription factors that affect the ability of RNA polymerase to begin the transcription process may work by ______.

regulating the binding of the transcriptional complex to the core promoter controlling the switch from the initiation to the elongation stage of transcription

Chromatin is a very dynamic structure that can alternate between two conformations

•Closed conformation Chromatin is very tightly packed Transcription may be difficult or impossible •Open conformation Chromatin is accessible to transcription factors Transcription can take place

Common factors contributing to combinatorial control are

•One or more activator proteins may stimulate transcription •One or more repressor proteins may inhibit transcription

•Gonadocorticoids

•These include estrogen and testosterone •They influence the growth and function of the gonads

•Glucocorticoids

•These influence nutrient metabolism in most cells •They promote glucose utilization, fat mobilization and protein breakdown

Activators and repressors may be modulated by:

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