Upload
vincent-hardy
View
221
Download
0
Tags:
Embed Size (px)
Citation preview
CH. 11 : CH. 11 : Transcriptional Transcriptional Control of Gene Control of Gene
ExpressionExpression
Jennifer BrownJennifer Brown
INTRODUCTIONINTRODUCTION
Gene expression: the entire process Gene expression: the entire process whereby the information in a particular whereby the information in a particular gene gene is decoded into a particular is decoded into a particular protein.protein.
RNA polymerase is required to initiate RNA polymerase is required to initiate transcriptiontranscription
mRNA is then synthesized at a certain site, mRNA is then synthesized at a certain site, transported from the nucleus to cytoplasm, transported from the nucleus to cytoplasm, then translated into proteinthen translated into protein
Ribosomes, tRNA, and translation factors all Ribosomes, tRNA, and translation factors all aid in this processaid in this process
Control of Transcription Control of Transcription InitiationInitiation
This is the first step and most important This is the first step and most important mechanism for determining whether genes are mechanism for determining whether genes are expressed and how much of encoded mRNAs expressed and how much of encoded mRNAs (proteins) are produced(proteins) are produced
Gene control allows for the correct expression Gene control allows for the correct expression of the correct genes during developmentof the correct genes during development
Regulation of transcription initiation is most Regulation of transcription initiation is most widespread form of gene controlwidespread form of gene control
Transcription PromotersTranscription Promoters
The promoter is the DNA sequence that The promoter is the DNA sequence that specifies where transcription beginsspecifies where transcription begins
Transcription factors may bind upstream Transcription factors may bind upstream or downstream from the promoteror downstream from the promoter
This allows for complex control of gene This allows for complex control of gene expressionexpression
RNA PolymerasesRNA Polymerases
Eukaryotic cells contain three different RNA Eukaryotic cells contain three different RNA polymerases which contain 2 large and 3 small polymerases which contain 2 large and 3 small core subunitscore subunits
RNA polymerase I is located in the nucleolus RNA polymerase I is located in the nucleolus and transcribes genes encoding pre-rRNA and transcribes genes encoding pre-rRNA which is processed into 28S, 5.8S, and 18S which is processed into 28S, 5.8S, and 18S rRNAsrRNAs
RNA polymerase III transcribes genes RNA polymerase III transcribes genes encoding tRNA, 5S rRNA, and other small encoding tRNA, 5S rRNA, and other small stable RNAsstable RNAs
RNA Polymerase IIRNA Polymerase II
Transcribes ALL protein-coding genes and Transcribes ALL protein-coding genes and function in production of mRNAsfunction in production of mRNAs
Contains a carboxyl-terminal domain which the Contains a carboxyl-terminal domain which the other two do not haveother two do not have
Carboxyl end of largest subunit contains a Carboxyl end of largest subunit contains a stretch of 7 amino acidsstretch of 7 amino acids
This sequence Tyr-Ser-Pro-Thr-Ser-Pro-Ser is This sequence Tyr-Ser-Pro-Thr-Ser-Pro-Ser is repeated multiple timesrepeated multiple times
Also initiates transcription of genes at the DNA Also initiates transcription of genes at the DNA sequence encoding the capped 5’ end of the sequence encoding the capped 5’ end of the mRNAmRNA
Transcription-Control Transcription-Control RegionsRegions
Protein-binding DNA sequences that Protein-binding DNA sequences that regulate protein-coding genesregulate protein-coding genes
Promoter: control elements plus TATA-Promoter: control elements plus TATA-box or initiator box or initiator
Enhancers: long distance transcriptional-Enhancers: long distance transcriptional-control elements which can occur control elements which can occur upstream or downstream from a upstream or downstream from a promoter and are cell-type specificpromoter and are cell-type specific
Types of Promoter Types of Promoter Sequences in Eukaryotic Sequences in Eukaryotic
DNADNA 3 Types3 Types TATA box: this is the most common type found TATA box: this is the most common type found
upstream from start site and rapidly transcribes upstream from start site and rapidly transcribes genesgenes
Initiators: these have cytosine at -1 position Initiators: these have cytosine at -1 position and adenine at start site (+1)and adenine at start site (+1)
CpG Islands: located upstream from start site CpG Islands: located upstream from start site and have low rate of transcribed genesand have low rate of transcribed genes
TATA BOX TATA BOX
Transcription FactorsTranscription Factors
Activate or repress expression of protein-Activate or repress expression of protein-coding genescoding genes Example is GAL4 which is composed of a N-Example is GAL4 which is composed of a N-
terminus DNA-binding domain and a C-terminus DNA-binding domain and a C-terminus activation domainterminus activation domain
Transcription repressors are functionally Transcription repressors are functionally converse of activatorsconverse of activators
Classes of DNA Binding Classes of DNA Binding ProteinsProteins
Homeodomain Proteins: contain conserved 60-Homeodomain Proteins: contain conserved 60-residue DNA-binding motifresidue DNA-binding motif
Zinc-Finger Proteins: regions fold around a Zinc-Finger Proteins: regions fold around a central Zinc ion and produce compact domain central Zinc ion and produce compact domain from short polypeptide chainfrom short polypeptide chain
Leucine-Zipper Proteins: contain the amino Leucine-Zipper Proteins: contain the amino acid Leucine at every 7acid Leucine at every 7thth position and bind to position and bind to DNA as dimersDNA as dimers
Basic Helix-Loop-Helix Proteins: similar in Basic Helix-Loop-Helix Proteins: similar in structure to basic-zipper motifstructure to basic-zipper motif
DNA-BINDING PROTEINSDNA-BINDING PROTEINS
Heterodimeric Heterodimeric Transcription FactorsTranscription Factors
Allow activation domains of each Allow activation domains of each monomer to be placed together in monomer to be placed together in different combinationsdifferent combinations
Each monomer with different DNA-Each monomer with different DNA-binding specificity increases number of binding specificity increases number of DNA sequences the family of DNA sequences the family of transcription factors can bindtranscription factors can bind
Allows for combinatorial complexityAllows for combinatorial complexity
Transcription Initiation Transcription Initiation by RNA Polymerase IIby RNA Polymerase II
General Transcription Factors: initiation General Transcription Factors: initiation factors that place polymerase molecules factors that place polymerase molecules at transcription start sites and help at transcription start sites and help template strand enter active site template strand enter active site Example in Polymerase II: TFIIA, TFIIB, etc.Example in Polymerase II: TFIIA, TFIIB, etc.
Required for synthesis of RNA from most Required for synthesis of RNA from most genesgenes
TRANSCRIPTION TRANSCRIPTION FACTORSFACTORS
Regulatory ProteinsRegulatory Proteins
Act in concert with other proteins to Act in concert with other proteins to modulate chromatin structure modulate chromatin structure This influences ability of transcription factors This influences ability of transcription factors
to bind to promotersto bind to promoters Also interact with large multiprotein Also interact with large multiprotein
complex = mediatorcomplex = mediator This binds with Pol II and directly regulates This binds with Pol II and directly regulates
assembly of transcription preinitiation assembly of transcription preinitiation complexescomplexes
Regulation of Transcription-Regulation of Transcription-Factor ActivityFactor Activity
Expression of transcription factor by a Expression of transcription factor by a cell is regulatedcell is regulated
Activities of those factors expressed are Activities of those factors expressed are also controlled indirectlyalso controlled indirectly
This is done by interaction between This is done by interaction between proteins on surface of cell and by proteins on surface of cell and by external hormones and growth factorsexternal hormones and growth factors
Nuclear ReceptorsNuclear Receptors
All have unique N-terminal regionAll have unique N-terminal region Response elements bind several nuclear Response elements bind several nuclear
receptors and can be:receptors and can be: InvertedInverted Direct repeatsDirect repeats Heterodimeric:located exclusively in nucleusHeterodimeric:located exclusively in nucleus Homodimeric: found in cytoplasm in Homodimeric: found in cytoplasm in
absence of ligansabsence of ligans
Mechanisms for Mechanisms for Terminating Terminating TranscriptionTranscription
Differ for each of 3 RNA PolymerasesDiffer for each of 3 RNA Polymerases RNA Polymerase I: termination requires RNA Polymerase I: termination requires
polymerase-specific termination factorpolymerase-specific termination factor RNA Polymerase II: terminates after RNA Polymerase II: terminates after
polymerizing a series of U residuespolymerizing a series of U residues RNA Polymerase III: doesn’t terminate until RNA Polymerase III: doesn’t terminate until
after a sequence is transcribed that directs after a sequence is transcribed that directs cleavage and polyadenylation of RNAcleavage and polyadenylation of RNA
QUESTIONS???QUESTIONS???