B2.080 Regulating the Activity of Transcription Factors Flashcards
what mechanisms can be used to regulate transcription factors?
developmentally
ligands
post translational modification
describe developmental regulation of TFs
some TFs are ubiquitously expressed, some are cell type specific
expression of lineage specific TFs drive cell lineage fate
what are the lineage determining factors for cardiomyocytes?
NKX2-5 GATA4 TBX2 TBX5 Baf60c
How are cytoplasm resident nuclear hormone receptors activated?
ligand binds and facilitates movement into nucleus
TF is then free to bind DNA and recruit co-activators to help initiate transcription
what determines which enzymes a nuclear hormone receptor (NHR) binds?
tissue where NHR is acting
many remodeling complexes have different expression in different tissues
characterize selective estrogen receptor modulator drugs (SERMs)
have mixed agonist and antagonist activity
based upon tissue-specific interactions between ER and HATS/HDACs/CRCs
how are nuclear resident nuclear hormone receptors regulated?
normal binding to DNA exhibits repressive effect
when ligand binds to receptor, HDAC is released and HATs/CRCs are recruited
what are example cytoplasm resident and nuclear resident NHRs?
cyto: glucocorticoid & estrogen receptors
nuclear: thyroid hormone, vitamin D, & retinoic acid receptors
what are examples of post translational modifications that can increase/decrease TF activity?
phosphorylation, acetylation, methylation, etc.
what are 4 schemes of post translational modification regulation of TFs
- TF bound to anchor protein in cytoplasm, modification released TF to nucleus
- TF is resident in cytoplasm, modification directly sends it to the nucleus
- TF is bound to DNA, modification alters function (binding partners)
- TF stability is affected by modification
describe the nuclear factor kappa B pathway
bacteria surface molecules bind to cell receptors
signally cascade activated a kinase which phosphorylated IKB, releasing NFkB
NFkB moves to nucleus and upregulated genes coding for an immunoresponse