Table 1

1
Table 1 Complexes Involved in RNApII PIC
assembly. Protein complex Functions RNApII
12 Subunits catalyzes transcription of all
mRNAs and a subset of noncoding RNAs including
snoRNAs and miRNAs TFIIA 23 subunits
functions to counteract repressive effects of
negative cofactors like NC2 acts as a
coactivator by interacting with activators and
components of the basal initiation
machinery TFIIB Single subunit stabilizes
TFIID-promoter binding aids in recruitment of
TFIIF/Pol II to the promoter directs accurate
start site selection TFIID 14 subunits
including TBP and TBP Associated Factors (TAFs)
nucleates PIC assembly either through TBP
binding to TATA sequences or TAF binding to other
promoter sequences coactivator activity through
direct interaction of TAFs and gene specific
activators TFIIE 2 subunits helps recruit
TFIIH to promoters stimulates helicase and
kinase activities of TFIIH binds ssDNA and is
essential for promoter melting TFIIF 23
subunits tightly associates with RNApII
enhances affinity of RNApII for
TBP-TFIIB-promoter complex necessary for
recruitment of TFIIE/TFIIH to the PIC aids in
start site selection and promoter escape
enhances elongation efficiency TFIIH 10
subunits ATPase/helicase necessary for promoter
opening and promoter clearance helicase activity
for transcription coupled DNA repair kinase
activity required for phosphorylation of RNApII
CTD facilitates transition from initiation to
elongation Mediator At least 24 subunits
bridges interaction between activators and basal
factors stimulates both activator dependent
and basal transcription required for
transcription from most RNApII dependent
promoters SAGA 20 subunits interacts with
activators, histone H3, and TBP histone
acetyltransferase activity deubiquitinating
activity Trf1 TBP related factor identified in
Drosophila upregulated in CNS and gonads during
development can bind TATA sequences mostly
found at RNApIII dependent promoters as part of
TFIIIB but also required at a subset of RNApII
dependent promoters Trf2 TBP related factor
identified in all metazoans cannot bind TATA
sequences important for histone gene
expression in Drosophila Trf3 TBP related
factor identified in vertebrates can bind TATA
sequences important for differentiation of
muscle cells in mammals and for haematopoietic
cell development in zebrafish. TFIIS 1 subunit
stimulates intrinsic transcript cleavage activity
of RNApII allowing backtracking to resume RNA
synthesis after transcription arrest
stimulates PIC assembly at some promoters NC2 2
subunits binds TBP/DNA complexes and blocks PIC
assembly can have both positive and negative
effects on transcription Mot1/bTAF1 1
subunit induces dissociation of TBP/DNA
complexes in ATP dependent manner can have both
positive and negative effects on transcription
2
PIC Pre-initiation complex this is the
business end of the transcription apparatus.
Questions

1. How does the PIC decide where to form?
2. Why isnt the PIC sufficient for efficient gene
   expression?
3. How are PIC assembly and transcriptional
   activation controlled?

3
Table 1 Complexes Involved in RNApII PIC
assembly. Protein complex Functions RNApII
12 Subunits catalyzes transcription of all
mRNAs and a subset of noncoding RNAs including
snoRNAs and miRNAs TFIIA 23 subunits
functions to counteract repressive effects of
negative cofactors like NC2 acts as a
coactivator by interacting with activators and
components of the basal initiation
machinery TFIIB Single subunit stabilizes
TFIID-promoter binding aids in recruitment of
TFIIF/Pol II to the promoter directs accurate
start site selection TFIID 14 subunits
including TBP and TBP Associated Factors (TAFs)
nucleates PIC assembly either through TBP
binding to TATA sequences or TAF binding to other
promoter sequences coactivator activity through
direct interaction of TAFs and gene specific
activators TFIIE 2 subunits helps recruit
TFIIH to promoters stimulates helicase and
kinase activities of TFIIH binds ssDNA and is
essential for promoter melting TFIIF 23
subunits tightly associates with RNApII
enhances affinity of RNApII for
TBP-TFIIB-promoter complex necessary for
recruitment of TFIIE/TFIIH to the PIC aids in
start site selection and promoter escape
enhances elongation efficiency TFIIH 10
subunits ATPase/helicase necessary for promoter
opening and promoter clearance helicase activity
for transcription coupled DNA repair kinase
activity required for phosphorylation of RNApII
CTD facilitates transition from initiation to
elongation Mediator At least 24 subunits
bridges interaction between activators and basal
factors stimulates both activator dependent
and basal transcription required for
transcription from most RNApII dependent
promoters SAGA 20 subunits interacts with
activators, histone H3, and TBP histone
acetyltransferase activity deubiquitinating
activity Trf1 TBP related factor identified in
Drosophila upregulated in CNS and gonads during
development can bind TATA sequences mostly
found at RNApIII dependent promoters as part of
TFIIIB but also required at a subset of RNApII
dependent promoters Trf2 TBP related factor
identified in all metazoans cannot bind TATA
sequences important for histone gene
expression in Drosophila Trf3 TBP related
factor identified in vertebrates can bind TATA
sequences important for differentiation of
muscle cells in mammals and for haematopoietic
cell development in zebrafish. TFIIS 1 subunit
stimulates intrinsic transcript cleavage activity
of RNApII allowing backtracking to resume RNA
synthesis after transcription arrest
stimulates PIC assembly at some promoters NC2 2
subunits binds TBP/DNA complexes and blocks PIC
assembly can have both positive and negative
effects on transcription Mot1/bTAF1 1
subunit induces dissociation of TBP/DNA
complexes in ATP dependent manner can have both
positive and negative effects on transcription
4
Image from euchromatin.org
5
Gnatt et al, (2001) Science, vol 292, 1876-1882
6
Table 1 Complexes Involved in RNApII PIC
assembly. Protein complex Functions RNApII
12 Subunits catalyzes transcription of all
mRNAs and a subset of noncoding RNAs including
snoRNAs and miRNAs TFIIA 23 subunits
functions to counteract repressive effects of
negative cofactors like NC2 acts as a
coactivator by interacting with activators and
components of the basal initiation
machinery TFIIB Single subunit stabilizes
TFIID-promoter binding aids in recruitment of
TFIIF/Pol II to the promoter directs accurate
start site selection TFIID 14 subunits
including TBP and TBP Associated Factors (TAFs)
nucleates PIC assembly either through TBP
binding to TATA sequences or TAF binding to other
promoter sequences coactivator activity through
direct interaction of TAFs and gene specific
activators TFIIE 2 subunits helps recruit
TFIIH to promoters stimulates helicase and
kinase activities of TFIIH binds ssDNA and is
essential for promoter melting TFIIF 23
subunits tightly associates with RNApII
enhances affinity of RNApII for
TBP-TFIIB-promoter complex necessary for
recruitment of TFIIE/TFIIH to the PIC aids in
start site selection and promoter escape
enhances elongation efficiency TFIIH 10
subunits ATPase/helicase necessary for promoter
opening and promoter clearance helicase activity
for transcription coupled DNA repair kinase
activity required for phosphorylation of RNApII
CTD facilitates transition from initiation to
elongation Mediator At least 24 subunits
bridges interaction between activators and basal
factors stimulates both activator dependent
and basal transcription required for
transcription from most RNApII dependent
promoters SAGA 20 subunits interacts with
activators, histone H3, and TBP histone
acetyltransferase activity deubiquitinating
activity Trf1 TBP related factor identified in
Drosophila upregulated in CNS and gonads during
development can bind TATA sequences mostly
found at RNApIII dependent promoters as part of
TFIIIB but also required at a subset of RNApII
dependent promoters Trf2 TBP related factor
identified in all metazoans cannot bind TATA
sequences important for histone gene
expression in Drosophila Trf3 TBP related
factor identified in vertebrates can bind TATA
sequences important for differentiation of
muscle cells in mammals and for haematopoietic
cell development in zebrafish. TFIIS 1 subunit
stimulates intrinsic transcript cleavage activity
of RNApII allowing backtracking to resume RNA
synthesis after transcription arrest
stimulates PIC assembly at some promoters NC2 2
subunits binds TBP/DNA complexes and blocks PIC
assembly can have both positive and negative
effects on transcription Mot1/bTAF1 1
subunit induces dissociation of TBP/DNA
complexes in ATP dependent manner can have both
positive and negative effects on transcription
7
Eukaryotic Basal DNA elements
TATA element (TATA) Initiator element
(INR) Downstream Promoter element (DPE) TFIIB
recognition element (BRE)
Any given eukaryotic promoter will have one or
more of these elements, but seldom all of them.
The PIC can thus be recruited to different
promoters in different Ways.
8
(No Transcript)
9
Table 1 Complexes Involved in RNApII PIC
assembly. Protein complex Functions RNApII
12 Subunits catalyzes transcription of all
mRNAs and a subset of noncoding RNAs including
snoRNAs and miRNAs TFIIA 23 subunits
functions to counteract repressive effects of
negative cofactors like NC2 acts as a
coactivator by interacting with activators and
components of the basal initiation
machinery TFIIB Single subunit stabilizes
TFIID-promoter binding aids in recruitment of
TFIIF/Pol II to the promoter directs accurate
start site selection TFIID 14 subunits
including TBP and TBP Associated Factors (TAFs)
nucleates PIC assembly either through TBP
binding to TATA sequences or TAF binding to other
promoter sequences coactivator activity through
direct interaction of TAFs and gene specific
activators TFIIE 2 subunits helps recruit
TFIIH to promoters stimulates helicase and
kinase activities of TFIIH binds ssDNA and is
essential for promoter melting TFIIF 23
subunits tightly associates with RNApII
enhances affinity of RNApII for
TBP-TFIIB-promoter complex necessary for
recruitment of TFIIE/TFIIH to the PIC aids in
start site selection and promoter escape
enhances elongation efficiency TFIIH 10
subunits ATPase/helicase necessary for promoter
opening and promoter clearance helicase activity
for transcription coupled DNA repair kinase
activity required for phosphorylation of RNApII
CTD facilitates transition from initiation to
elongation Mediator At least 24 subunits
bridges interaction between activators and basal
factors stimulates both activator dependent
and basal transcription required for
transcription from most RNApII dependent
promoters SAGA 20 subunits interacts with
activators, histone H3, and TBP histone
acetyltransferase activity deubiquitinating
activity Trf1 TBP related factor identified in
Drosophila upregulated in CNS and gonads during
development can bind TATA sequences mostly
found at RNApIII dependent promoters as part of
TFIIIB but also required at a subset of RNApII
dependent promoters Trf2 TBP related factor
identified in all metazoans cannot bind TATA
sequences important for histone gene
expression in Drosophila Trf3 TBP related
factor identified in vertebrates can bind TATA
sequences important for differentiation of
muscle cells in mammals and for haematopoietic
cell development in zebrafish. TFIIS 1 subunit
stimulates intrinsic transcript cleavage activity
of RNApII allowing backtracking to resume RNA
synthesis after transcription arrest
stimulates PIC assembly at some promoters NC2 2
subunits binds TBP/DNA complexes and blocks PIC
assembly can have both positive and negative
effects on transcription Mot1/bTAF1 1
subunit induces dissociation of TBP/DNA
complexes in ATP dependent manner can have both
positive and negative effects on transcription
10
TFIID
TFIID is a major player in transcriptional
initiation. Thought to nucleate PIC assembly
through TBP binding to DNA. Its composition can
change depending on which subunits are included
(see next fig). About 10 of genes are
dependent on SAGA rather than TFIID. SAGA TFIID
are probably homologous. SAGA also includes
TBP. Is TFIID required for every round of
transcription?
11
Cler et al, (2009) Cell Mol Lif Sci, vol 66,
2123-2134
12
(No Transcript)
13
Table 1 Complexes Involved in RNApII PIC
assembly. Protein complex Functions RNApII
12 Subunits catalyzes transcription of all
mRNAs and a subset of noncoding RNAs including
snoRNAs and miRNAs TFIIA 23 subunits
functions to counteract repressive effects of
negative cofactors like NC2 acts as a
coactivator by interacting with activators and
components of the basal initiation
machinery TFIIB Single subunit stabilizes
TFIID-promoter binding aids in recruitment of
TFIIF/Pol II to the promoter directs accurate
start site selection TFIID 14 subunits
including TBP and TBP Associated Factors (TAFs)
nucleates PIC assembly either through TBP
binding to TATA sequences or TAF binding to other
promoter sequences coactivator activity through
direct interaction of TAFs and gene specific
activators TFIIE 2 subunits helps recruit
TFIIH to promoters stimulates helicase and
kinase activities of TFIIH binds ssDNA and is
essential for promoter melting TFIIF 23
subunits tightly associates with RNApII
enhances affinity of RNApII for
TBP-TFIIB-promoter complex necessary for
recruitment of TFIIE/TFIIH to the PIC aids in
start site selection and promoter escape
enhances elongation efficiency TFIIH 10
subunits ATPase/helicase necessary for promoter
opening and promoter clearance helicase activity
for transcription coupled DNA repair kinase
activity required for phosphorylation of RNApII
CTD facilitates transition from initiation to
elongation Mediator At least 24 subunits
bridges interaction between activators and basal
factors stimulates both activator dependent
and basal transcription required for
transcription from most RNApII dependent
promoters SAGA 20 subunits interacts with
activators, histone H3, and TBP histone
acetyltransferase activity deubiquitinating
activity Trf1 TBP related factor identified in
Drosophila upregulated in CNS and gonads during
development can bind TATA sequences mostly
found at RNApIII dependent promoters as part of
TFIIIB but also required at a subset of RNApII
dependent promoters Trf2 TBP related factor
identified in all metazoans cannot bind TATA
sequences important for histone gene
expression in Drosophila Trf3 TBP related
factor identified in vertebrates can bind TATA
sequences important for differentiation of
muscle cells in mammals and for haematopoietic
cell development in zebrafish. TFIIS 1 subunit
stimulates intrinsic transcript cleavage activity
of RNApII allowing backtracking to resume RNA
synthesis after transcription arrest
stimulates PIC assembly at some promoters NC2 2
subunits binds TBP/DNA complexes and blocks PIC
assembly can have both positive and negative
effects on transcription Mot1/bTAF1 1
subunit induces dissociation of TBP/DNA
complexes in ATP dependent manner can have both
positive and negative effects on transcription
14
TFIIH
TFIIH has three enzymatic activities 2
helicases (for promoter opening and for DNA
repair) 1 kinase (for phosphorylating CTD of RNA
pol II) Involved in transitioning from
initiation to elongation.
15
Keep in mind
Basal transcription factors (ie PIC) dont
transcribe chromatin templates. Basal
transcription factors dont respond to
activators. This raises the level of complexity,
and provides avenues for regulation, in two
ways. See upcoming lectures by Whitehouse
(chromatin) DiGregorio and Pertsinidis
(activators and regulatory modules)
16
Table 1 Complexes Involved in RNApII PIC
assembly. Protein complex Functions RNApII
12 Subunits catalyzes transcription of all
mRNAs and a subset of noncoding RNAs including
snoRNAs and miRNAs TFIIA 23 subunits
functions to counteract repressive effects of
negative cofactors like NC2 acts as a
coactivator by interacting with activators and
components of the basal initiation
machinery TFIIB Single subunit stabilizes
TFIID-promoter binding aids in recruitment of
TFIIF/Pol II to the promoter directs accurate
start site selection TFIID 14 subunits
including TBP and TBP Associated Factors (TAFs)
nucleates PIC assembly either through TBP
binding to TATA sequences or TAF binding to other
promoter sequences coactivator activity through
direct interaction of TAFs and gene specific
activators TFIIE 2 subunits helps recruit
TFIIH to promoters stimulates helicase and
kinase activities of TFIIH binds ssDNA and is
essential for promoter melting TFIIF 23
subunits tightly associates with RNApII
enhances affinity of RNApII for
TBP-TFIIB-promoter complex necessary for
recruitment of TFIIE/TFIIH to the PIC aids in
start site selection and promoter escape
enhances elongation efficiency TFIIH 10
subunits ATPase/helicase necessary for promoter
opening and promoter clearance helicase activity
for transcription coupled DNA repair kinase
activity required for phosphorylation of RNApII
CTD facilitates transition from initiation to
elongation Mediator At least 24 subunits
bridges interaction between activators and basal
factors stimulates both activator dependent
and basal transcription required for
transcription from most RNApII dependent
promoters SAGA 20 subunits interacts with
activators, histone H3, and TBP histone
acetyltransferase activity deubiquitinating
activity Trf1 TBP related factor identified in
Drosophila upregulated in CNS and gonads during
development can bind TATA sequences mostly
found at RNApIII dependent promoters as part of
TFIIIB but also required at a subset of RNApII
dependent promoters Trf2 TBP related factor
identified in all metazoans cannot bind TATA
sequences important for histone gene
expression in Drosophila Trf3 TBP related
factor identified in vertebrates can bind TATA
sequences important for differentiation of
muscle cells in mammals and for haematopoietic
cell development in zebrafish. TFIIS 1 subunit
stimulates intrinsic transcript cleavage activity
of RNApII allowing backtracking to resume RNA
synthesis after transcription arrest
stimulates PIC assembly at some promoters NC2 2
subunits binds TBP/DNA complexes and blocks PIC
assembly can have both positive and negative
effects on transcription Mot1/bTAF1 1
subunit induces dissociation of TBP/DNA
complexes in ATP dependent manner can have both
positive and negative effects on transcription
17
Mediator
Basal Factor or not? Not required for basal
activity in vitro, but it can stimulate this
activity. It has been proposed to stimulate
phosphorylation of the CTD of RNA pol II (see
Shuman lecture). Its composition can change
depending on which subunits are included
(again). Might also act by stimulating
reinitiation.
18
DAlessio et al, (2009) Mol Cell, vol 36, 924-931
19
Table 1 Complexes Involved in RNApII PIC
assembly. Protein complex Functions RNApII
12 Subunits catalyzes transcription of all
mRNAs and a subset of noncoding RNAs including
snoRNAs and miRNAs TFIIA 23 subunits
functions to counteract repressive effects of
negative cofactors like NC2 acts as a
coactivator by interacting with activators and
components of the basal initiation
machinery TFIIB Single subunit stabilizes
TFIID-promoter binding aids in recruitment of
TFIIF/Pol II to the promoter directs accurate
start site selection TFIID 14 subunits
including TBP and TBP Associated Factors (TAFs)
nucleates PIC assembly either through TBP
binding to TATA sequences or TAF binding to other
promoter sequences coactivator activity through
direct interaction of TAFs and gene specific
activators TFIIE 2 subunits helps recruit
TFIIH to promoters stimulates helicase and
kinase activities of TFIIH binds ssDNA and is
essential for promoter melting TFIIF 23
subunits tightly associates with RNApII
enhances affinity of RNApII for
TBP-TFIIB-promoter complex necessary for
recruitment of TFIIE/TFIIH to the PIC aids in
start site selection and promoter escape
enhances elongation efficiency TFIIH 10
subunits ATPase/helicase necessary for promoter
opening and promoter clearance helicase activity
for transcription coupled DNA repair kinase
activity required for phosphorylation of RNApII
CTD facilitates transition from initiation to
elongation Mediator At least 24 subunits
bridges interaction between activators and basal
factors stimulates both activator dependent
and basal transcription required for
transcription from most RNApII dependent
promoters SAGA 20 subunits interacts with
activators, histone H3, and TBP histone
acetyltransferase activity deubiquitinating
activity Trf1 TBP related factor identified in
Drosophila upregulated in CNS and gonads during
development can bind TATA sequences mostly
found at RNApIII dependent promoters as part of
TFIIIB but also required at a subset of RNApII
dependent promoters Trf2 TBP related factor
identified in all metazoans cannot bind TATA
sequences important for histone gene
expression in Drosophila Trf3 TBP related
factor identified in vertebrates can bind TATA
sequences important for differentiation of
muscle cells in mammals and for haematopoietic
cell development in zebrafish. TFIIS 1 subunit
stimulates intrinsic transcript cleavage activity
of RNApII allowing backtracking to resume RNA
synthesis after transcription arrest
stimulates PIC assembly at some promoters NC2 2
subunits binds TBP/DNA complexes and blocks PIC
assembly can have both positive and negative
effects on transcription Mot1/bTAF1 1
subunit induces dissociation of TBP/DNA
complexes in ATP dependent manner can have both
positive and negative effects on transcription
20
SAGA
Our first mention of histone modifying activity.
As mentioned earlier, can substitute (and might
be related to) TFIID. Like Mediator, it can
interact with both activators and TBP, acting
as a bridging molecule.
21
Baker and Grant, (2007) Oncogene, vol 26,
5329-5340
22
Table 1 Complexes Involved in RNApII PIC
assembly. Protein complex Functions RNApII
12 Subunits catalyzes transcription of all
mRNAs and a subset of noncoding RNAs including
snoRNAs and miRNAs TFIIA 23 subunits
functions to counteract repressive effects of
negative cofactors like NC2 acts as a
coactivator by interacting with activators and
components of the basal initiation
machinery TFIIB Single subunit stabilizes
TFIID-promoter binding aids in recruitment of
TFIIF/Pol II to the promoter directs accurate
start site selection TFIID 14 subunits
including TBP and TBP Associated Factors (TAFs)
nucleates PIC assembly either through TBP
binding to TATA sequences or TAF binding to other
promoter sequences coactivator activity through
direct interaction of TAFs and gene specific
activators TFIIE 2 subunits helps recruit
TFIIH to promoters stimulates helicase and
kinase activities of TFIIH binds ssDNA and is
essential for promoter melting TFIIF 23
subunits tightly associates with RNApII
enhances affinity of RNApII for
TBP-TFIIB-promoter complex necessary for
recruitment of TFIIE/TFIIH to the PIC aids in
start site selection and promoter escape
enhances elongation efficiency TFIIH 10
subunits ATPase/helicase necessary for promoter
opening and promoter clearance helicase activity
for transcription coupled DNA repair kinase
activity required for phosphorylation of RNApII
CTD facilitates transition from initiation to
elongation Mediator At least 24 subunits
bridges interaction between activators and basal
factors stimulates both activator dependent
and basal transcription required for
transcription from most RNApII dependent
promoters SAGA 20 subunits interacts with
activators, histone H3, and TBP histone
acetyltransferase activity deubiquitinating
activity Trf1 TBP related factor identified in
Drosophila upregulated in CNS and gonads during
development can bind TATA sequences mostly
found at RNApIII dependent promoters as part of
TFIIIB but also required at a subset of RNApII
dependent promoters Trf2 TBP related factor
identified in all metazoans cannot bind TATA
sequences important for histone gene
expression in Drosophila Trf3 TBP related
factor identified in vertebrates can bind TATA
sequences important for differentiation of
muscle cells in mammals and for haematopoietic
cell development in zebrafish. TFIIS 1 subunit
stimulates intrinsic transcript cleavage activity
of RNApII allowing backtracking to resume RNA
synthesis after transcription arrest
stimulates PIC assembly at some promoters NC2 2
subunits binds TBP/DNA complexes and blocks PIC
assembly can have both positive and negative
effects on transcription Mot1/bTAF1 1
subunit induces dissociation of TBP/DNA
complexes in ATP dependent manner can have both
positive and negative effects on transcription
23
TFIIS
Originally characterized as an elongation factor,
however more recently shown to play a role in
initiation and PIC formation as well.
24
Prather et al, (2005) Mol Cell Biol, vol 25,
2650-2659
25
Table 1 Complexes Involved in RNApII PIC
assembly. Protein complex Functions RNApII
12 Subunits catalyzes transcription of all
mRNAs and a subset of noncoding RNAs including
snoRNAs and miRNAs TFIIA 23 subunits
functions to counteract repressive effects of
negative cofactors like NC2 acts as a
coactivator by interacting with activators and
components of the basal initiation
machinery TFIIB Single subunit stabilizes
TFIID-promoter binding aids in recruitment of
TFIIF/Pol II to the promoter directs accurate
start site selection TFIID 14 subunits
including TBP and TBP Associated Factors (TAFs)
nucleates PIC assembly either through TBP
binding to TATA sequences or TAF binding to other
promoter sequences coactivator activity through
direct interaction of TAFs and gene specific
activators TFIIE 2 subunits helps recruit
TFIIH to promoters stimulates helicase and
kinase activities of TFIIH binds ssDNA and is
essential for promoter melting TFIIF 23
subunits tightly associates with RNApII
enhances affinity of RNApII for
TBP-TFIIB-promoter complex necessary for
recruitment of TFIIE/TFIIH to the PIC aids in
start site selection and promoter escape
enhances elongation efficiency TFIIH 10
subunits ATPase/helicase necessary for promoter
opening and promoter clearance helicase activity
for transcription coupled DNA repair kinase
activity required for phosphorylation of RNApII
CTD facilitates transition from initiation to
elongation Mediator At least 24 subunits
bridges interaction between activators and basal
factors stimulates both activator dependent
and basal transcription required for
transcription from most RNApII dependent
promoters SAGA 20 subunits interacts with
activators, histone H3, and TBP histone
acetyltransferase activity deubiquitinating
activity Trf1 TBP related factor identified in
Drosophila upregulated in CNS and gonads during
development can bind TATA sequences mostly
found at RNApIII dependent promoters as part of
TFIIIB but also required at a subset of RNApII
dependent promoters Trf2 TBP related factor
identified in all metazoans cannot bind TATA
sequences important for histone gene
expression in Drosophila Trf3 TBP related
factor identified in vertebrates can bind TATA
sequences important for differentiation of
muscle cells in mammals and for haematopoietic
cell development in zebrafish. TFIIS 1 subunit
stimulates intrinsic transcript cleavage activity
of RNApII allowing backtracking to resume RNA
synthesis after transcription arrest
stimulates PIC assembly at some promoters NC2 2
subunits binds TBP/DNA complexes and blocks PIC
assembly can have both positive and negative
effects on transcription Mot1/bTAF1 1
subunit induces dissociation of TBP/DNA
complexes in ATP dependent manner can have both
positive and negative effects on transcription
26
Repressors Mot1/bTAF1 and NC2
These proteins affect TBP/DNA binding by either
blocking PIC assembly or inducing dissociation
of TBP from the DNA. Counter-intuitively, these
can act as activators by preventing or
reducing in appropriate binding of PIC to
cryptic promoters, thus making more PIC
available for activation of appropriate
promoters.
27
van Werven et al, (2009) Genes and Development,
vol 22, 2259-2369
28
DAlessio et al, (2009) Mol Cell, vol 36, 924-931
29
Model of Regulated Recruitment
30
Potential mechanisms of transcriptional
activation

• Regulated Recruitment proteins bind to DNA and
  recruit an active
• polymerase complex to the promoter.

2. Polymerase Activation proteins bind to DNA
and activate a pre-bound, inactive
polymerase complex, thus initiating transcription.
3. Promoter Activation proteins bind to DNA and
induce a conformational change in the DNA,
twisting it into a active state that allows a
transcriptionally active polymerase can bind.
(Figures and concepts taken from Ptashne, M. and
Gann, A. (2002) Genes and Signals. Cold Spring
Harbor Laboratory Press, Cold Spring Harbor, New
York, USA.)