Download CH. 11 : Transcriptional Control of Gene Expression

CH. 11 :
Transcriptional
Control of Gene
Expression
Jennifer Brown
INTRODUCTION
 Gene expression: the entire process whereby
the information in a particular
gene is
decoded into a particular protein.
 RNA polymerase is required to initiate
transcription
 mRNA is then synthesized at a certain site,
transported from the nucleus to cytoplasm,
then translated into protein
 Ribosomes, tRNA, and translation factors all
aid in this process
Control of Transcription
Initiation
 This is the first step and most important
mechanism for determining whether genes are
expressed and how much of encoded mRNAs
(proteins) are produced
 Gene control allows for the correct expression
of the correct genes during development
 Regulation of transcription initiation is most
widespread form of gene control
Transcription Promoters
 The promoter is the DNA sequence that
specifies where transcription begins
 Transcription factors may bind upstream
or downstream from the promoter
 This allows for complex control of gene
expression
RNA Polymerases
 Eukaryotic cells contain three different RNA
polymerases which contain 2 large and 3 small
core subunits
 RNA polymerase I is located in the nucleolus
and transcribes genes encoding pre-rRNA
which is processed into 28S, 5.8S, and 18S
rRNAs
 RNA polymerase III transcribes genes
encoding tRNA, 5S rRNA, and other small
stable RNAs
RNA Polymerase II
 Transcribes ALL protein-coding genes and
function in production of mRNAs
 Contains a carboxyl-terminal domain which the
other two do not have
 Carboxyl end of largest subunit contains a
stretch of 7 amino acids
 This sequence Tyr-Ser-Pro-Thr-Ser-Pro-Ser is
repeated multiple times
 Also initiates transcription of genes at the DNA
sequence encoding the capped 5’ end of the
mRNA
Transcription-Control
Regions
 Protein-binding DNA sequences that
regulate protein-coding genes
 Promoter: control elements plus TATAbox or initiator
 Enhancers: long distance transcriptionalcontrol elements which can occur
upstream or downstream from a
promoter and are cell-type specific
Types of Promoter
Sequences in Eukaryotic
DNA
 3 Types
 TATA box: this is the most common type found
upstream from start site and rapidly transcribes
genes
 Initiators: these have cytosine at -1 position
and adenine at start site (+1)
 CpG Islands: located upstream from start site
and have low rate of transcribed genes
TATA BOX
Transcription Factors
 Activate or repress expression of proteincoding genes
 Example is GAL4 which is composed of a Nterminus DNA-binding domain and a Cterminus activation domain
 Transcription repressors are functionally
converse of activators
Classes of DNA Binding
Proteins
 Homeodomain Proteins: contain conserved 60residue DNA-binding motif
 Zinc-Finger Proteins: regions fold around a
central Zinc ion and produce compact domain
from short polypeptide chain
 Leucine-Zipper Proteins: contain the amino
acid Leucine at every 7th position and bind to
DNA as dimers
 Basic Helix-Loop-Helix Proteins: similar in
structure to basic-zipper motif
DNA-BINDING PROTEINS
Heterodimeric
Transcription Factors
 Allow activation domains of each
monomer to be placed together in
different combinations
 Each monomer with different DNAbinding specificity increases number of
DNA sequences the family of
transcription factors can bind
 Allows for combinatorial complexity
Transcription Initiation by
RNA Polymerase II
 General Transcription Factors: initiation
factors that place polymerase molecules
at transcription start sites and help
template strand enter active site
 Example in Polymerase II: TFIIA, TFIIB, etc.
 Required for synthesis of RNA from most
genes
TRANSCRIPTION
FACTORS
Regulatory Proteins
 Act in concert with other proteins to
modulate chromatin structure
 This influences ability of transcription factors
to bind to promoters
 Also interact with large multiprotein
complex = mediator
 This binds with Pol II and directly regulates
assembly of transcription preinitiation
complexes
Regulation of TranscriptionFactor Activity
 Expression of transcription factor by a
cell is regulated
 Activities of those factors expressed are
also controlled indirectly
 This is done by interaction between
proteins on surface of cell and by
external hormones and growth factors
Nuclear Receptors
 All have unique N-terminal region
 Response elements bind several nuclear
receptors and can be:




Inverted
Direct repeats
Heterodimeric:located exclusively in nucleus
Homodimeric: found in cytoplasm in
absence of ligans
Mechanisms for
Terminating Transcription
 Differ for each of 3 RNA Polymerases
 RNA Polymerase I: termination requires
polymerase-specific termination factor
 RNA Polymerase II: terminates after
polymerizing a series of U residues
 RNA Polymerase III: doesn’t terminate until
after a sequence is transcribed that directs
cleavage and polyadenylation of RNA
QUESTIONS???