Transcription III Flashcards
6 Ways to Regulate TF
Synthesis – target mRNA for degradation (AGO)
Access to DNA – euchromatin vs heterochromatin
Post-translational modifications – phosphorylation
Ligand Binding
Cellular Localization – cytoplasm vs nucleus
Availability of Co-activators
Nuclear Receptors Domains
1) N-terminal Regulatory Domain (AF-1)
- independent of ligand
2) DNA-Binding Domain (2 Zinc Fingers bind to HRE)
3) Hinge Region
4) Ligand Binding Domain (AF-2 – dependent on ligand)
- dimerization + co-activators
5) C-terminal Domain
Class I
Steroid Receptor (homodimer)
- receptor in cytoplasm bound to inhibitor (HSP)
- activate by steroid hormones –> translocate to nucleus
- bind to HRE = inverted repeats separated by 3 nts
= tissue development
Class I Receptors as Research Tools
Cre-recombinase = delete specific genes
Tamoxifen = remove HSP
- receptor enter nucleus at specific time
Class II
RXR Heterodimers
- receptor bound to gene in off state
- activate by metabolite/ligand passively enter nucleus
- bind as direct repeats separated by variable #of nts
= processing vitamins
Class II Function
switching genes from off –> on
co-repressor –> add ligand = co-activator
Class II in Development
Retinoic Acid
- without = co-repressor of Hox genes
- with = co-activator of Hox genes
—> needed in developmental processes (eyes/forelimbs)
Class III and IV
Dimeric Orphan Receptor
- homodimers + direct repeats
Monomeric Orphan Receptors
Nuclear Receptors in Cancer
diabetes, obesity, fibrosis, inflammation, angiogenesis