Chapter 12: Transcriptional Activators in Eukaryotes Flashcards
Jun & Fos (x4)
-AP1, specifically binds TGACTCA sequence (called?)
proto-oncogene proteins and cell signaling targets in bZIP family of activators; they dimerize
- dimerized form?
- tissue plasminogen activator (TPA) response element (TRE)
human metallothionine gene (x2)
example of multiple enhancers upstream of gene functioning cooperatively to regulate same gene
-uses glucocorticoid response element (GRE), basal level enhancer (BLE; AP1), and metal response element (MRE)
example of multiple enhancers upstream of gene functioning cooperatively to regulate same gene
-uses glucocorticoid response element (GRE), basal level enhancer (BLE; AP1), and metal response element (MRE)
human metallothionine gene (x2)
3 models of recruitment/activation
- sequential complex formation (binding by large pre-formed complex)
- RNA polymerase II holoenzyme
- combo of first 2
Endo 16 gene
- A activated
- G & B
- F & E
- DC
- F, E, & DC
basal promoter is activated in early development to form mesoderm tissues (muscle & skeleton)
- later, transcription is repressed to allow for development of ectoderm (CNS and skin)
1. early development (vegetal plate)
2. later development (mesoderm)
3. repression (ectoderm)
4. repression (skeletogenic mesenchyme)
5. LiCi treatment (ectoderm and skeletogenic mesenchyme)
Proteasome
- reduces concentration of (co)activators, providing additional transcriptional control
- e.g.?
large protein complex which breaks down/digests proteins to stop their function
- effect?
- e.g. LIM family of transcription factors can be tagged with ubiquitin and broken down inside cell
activator, directly phosphorylated by protein kinase A (PKA) from hormonal signals that act through receptors increasing cAMP levels
-dimerizes after phosphorylated b/c of shape change; stimulates transcription with CBP
CREB (cAMP response element [CRE]-binding protein)
2 categories of transcriptional activators
- e.g. zince finger (Sp1 & TFIIIA), homeodomain (HD) w/ helix-turn-helix (Lambda phage repressor), & bZIP and bHLH (Myo D)
- acidic, glutamine-rich, and proline-rich domains help drive RNA polymerase activation (e.g. CREB & Elk-1)
- DNA-binding
- structures? e.g? - transcription-activating domains
- structures? e.g.?
provided evidence for holoenzyme complexbeing recruited to promoter in yeast
- how?
- TFIID was not part of holoenzyme but recruited simultaneously with holoenzyme to promoter
Ptashne et al 1995
- GAL11-P (part of holoenzyme) could directly bind GAL4
- unique?
insulators (GAGA boxes)
type 1=enhancer-blocking: prevent enhancer or protein triggering transcription
- 2 methods?
- e.g. Tr1
type 2=blocking “gene silencing”: block chromatin from covering/interfering w/ gene expression
sequences of DNA that function to help control the specificity of gene expression (sequence?)
-2 types activity?
method 1=stop activator or other associated proteins from contacting promoter (blocks DABPolFEH) (e.g.?)
method 2=DNA looping by protein dimerization, preventing activator and enhancer from stimulating transcription
basal promoter is activated in early development to form mesoderm tissues (muscle & skeleton)
- later, transcription is repressed to allow for development of ectoderm (CNS and skin)
1. early development (vegetal plate)
2. later development (mesoderm)
3. repression (ectoderm)
4. repression (skeletogenic mesenchyme)
5. LiCi treatment (ectoderm and skeletogenic mesenchyme)
Endo 16 gene
- A activated
- G & B
- F & E
- DC
- F, E, & DC
bend DNA to enhance transcription by forming an enhanceosome
NF-kB, ATF
bind zinc and steroid hormones (i.e. ?) after which receptor complex (HR) moves into nucleus and activates transcription by binding hormone response elements (HREs) in the DNA
-3 types: types 1 & 2?
nuclear receptors
- i.e. testosterone, estrogen, & glucocorticoids
- 1=glucocorticoid; 2=thyroid hormone
coactivator with CREB, binds downstream of signaling events to regulate nerve cell development (synaptic plasticity)
- also coactivator for?
- with receptor and steroid receptor coactivators (SCR) to assemble transcription machinery and activate transcription
- additional function?
CBP
- hormone receptors and MAPK-response activators (ERK)
- interacts with?
- acetylate histone proteins to enhance gene transcription
NF-kB, ATF
bend DNA to enhance transcription by forming an enhanceosome
determined concentration of transcription factor proteins of yeast cell; found that weren’t in equal amounts
- suggests?
- discovered protein coactivators (mediators) in 1991 that further stimulate transcription that’s been activated by an activator (GAL4)
- how?
Kornberg et al (x2)
- preinitiation complex may assemble either as holoenzyme or in a sequence depending on promoter/gene
- used strand of DNA containing a promoter and GAL4-binding site and measured the synthesis of RNA in vitro
function to recruit & trigger transcription factor and polymerase binding to promoter: DNA-binding, transcription-activating, & dimerization
-essential preinitiation targets?
activators: 3 activator domains
- TFIID & TFIIB
- DNA-binding
- structures? e.g? - transcription-activating domains
- structures? e.g.?
2 categories of transcriptional activators
- e.g. zince finger (Sp1 & TFIIIA), homeodomain (HD) w/ helix-turn-helix (Lambda phage repressor), & bZIP and bHLH (Myo D)
- acidic, glutamine-rich, and proline-rich domains help drive RNA polymerase activation (e.g. CREB & Elk-1)
Kornberg et al (x2)
- preinitiation complex may assemble either as holoenzyme or in a sequence depending on promoter/gene
- used strand of DNA containing a promoter and GAL4-binding site and measured the synthesis of RNA in vitro
determined concentration of transcription factor proteins of yeast cell; found that weren’t in equal amounts
- suggests?
- discovered protein coactivators (mediators) in 1991 that further stimulate transcription that’s been activated by an activator (GAL4)
- how?
- increases affinity for DNA
- provides sustained DNA binding/transcription
- enhances their function at low concentrations
activator dimerization (x3)
glucocorticoid receptor (x3)
-Hsp90 released and receptor complex binds to glucocorticoid response elements (GREs)
type I receptor retained in cytoplasm by Hsp90 protein until it binds to glucocorticoid
- receptor complex associates with DNA via helical region and can dimerize w/ second receptor complex to activate transcription of hormonally-responsive genes
- hormone binding effect?
sequences of DNA that function to help control the specificity of gene expression (sequence?)
-2 types activity?
method 1=stop activator or other associated proteins from contacting promoter (blocks DABPolFEH) (e.g.?)
method 2=DNA looping by protein dimerization, preventing activator and enhancer from stimulating transcription
insulators (GAGA boxes)
type 1=enhancer-blocking: prevent enhancer or protein triggering transcription
- 2 methods?
- e.g. Tr1
type 2=blocking “gene silencing”: block chromatin from covering/interfering w/ gene expression
regulate transcription/gene expression to control growth, division, and metabolism
-e.g.?
signal transduction pathways
-e.g. extracellular growth factor (EGF) activating MAPK (ERK) pathway & gene transcription, causing cell growth and division
nuclear receptors
- i.e. testosterone, estrogen, & glucocorticoids
- 1=glucocorticoid; 2=thyroid hormone
bind zinc and steroid hormones (i.e. ?) after which receptor complex (HR) moves into nucleus and activates transcription by binding hormone response elements (HREs) in the DNA
-3 types: types 1 & 2?
