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Transcriptional Factor Families

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imissyou419's version from 2016-12-20 18:25

Section

Question Answer
Transcription factorDO NOT NEED TO BIND DNA, just affecting transcription in a postive or negative way
General transcription factorsinitiate gene expression, TFII proteins, bind all genes, RNA pol II is NOT a transcription factor (bind to all gnes that BECOME ACTIVE, active or primed)
Specific transcription factorsincrease transcription rate and EFFICIENCY for a specific gene, only binds to a specific gene but is required for COMPLETE expression of a gene (tissue specific, developmental specific)
Binds to enhancer regions or promoter so if mutated, get decrease in expression
Diseases involved in mutation in enhancer region where specific transcription factors bindget lowered expression (not complete loss) whereas general transcription factor give complete loss
Transcription factors have: DNA binding domain, transcriptional activation/repressor domain, NLS, ligand binding domain, domain for binding co-activators or co-repressors, binding domains for other TFs (not all in 1 transcription factor b/c want redundancy)
Transcription factors are classified based on theirprotein binding motifs
basic super classleucine zipper (ZIP), helix-loop-helix (HLH), HLH-ZIP
bHLH binds to the consensus DNA sequenceCANNTG (palindromic sequence), in a dimer, binds small groove of DNA/very specific (whereas helix turn helix bind larger region)
T/F - Protein binding on their own is not stableT - protein binding on its own is not stable, need mass interaction with DNA to stabilize conformation
Zinc-coordinating DNA-binding domainszinc fingers or zinc clusters, provide specificity for DNA sequences; (has Histidine and Cysteine which bind to Zn and hold it in place, dictating where protein will bind), can modify a.a. and manipulate expression to make protein bind to any sequence you want
Consensus sequence for zinc fingersF/Y - C - C - F/Y - H - H (2 cysteine, 2 histidine)
Helix-turn-helixhomeodomain, paired box, fork head, binds wider range of DNA
Beta-scaffold factorsSTAT, NFAT, P53, TATA binding protein
Other transcription factorsHMGB1 (don't worry about name) bends DNA to facilitate binding of other transcription factors (such as p53)
If you have a transcription factor without transactivation domain binding to the same consensus sequence as another transcription factor, what happens?Prevent transcription factor B from binding to consensus site so don't get transcription
Regulation of transcription factors - synthesis (transcription/translation)microRNA complementary to RNA bind to RNA and form dsRNA complex so prevent translation
Regulation of transcription factors - access to DNAheterochromatin prevent access of transcriptional factors whereas euchromatin is accessible for transcriptional activation (epigenetics regulate chromatin structure), controlled by histone modification and chromatin remodelling factors
Regulation of transcriptional factors - post-translational modifications, cellular localization, ligand binding
1) phosphorylated ERK
2) phosphorylated SMAD2/3
3) dephosphorylated b-catenin
ligand binding of receptor at cell surface trigger signalling event, post translational modification - phosphorylation occurs, changes in cell localization (cytoplasm -> nucleus) leads to binding with other TFs

1) phosphorylated ERK translocate into nucleus and phosphorylate multiple nuclear localized TFs
- MAPK phosphorylate Mitf, phosphorylated Mitf bind to id (repressor)which prevent it from binding to DNA
- p38 (another MAPK) inhibit ^ pathway and phosphorylated Mitf binds to PU1 and get expression
- bring NFAT which allows for better transcription
WHERE KINASE IS LOCALIZED IS BEING REGULATED, NOT TRANSCRIPTION FACTOR, IF KINASE DOES NOT GET INTO NUCLEUS - NO TRANSCRIPTION
2) phosphorylated SMAD2/3 binds to SMAD4 and it translocate to nucleus
LOCATION OF TRANSCRIPTION FACTOR IS REGULATED
3) phosphorylated B-catenin normally promotes degradation, when it is not phosphorylated through signal -> translocate to nucleus and bind to factor TCF, stabilize interaction and allow for expression
REGULATE LOCATION OF A TRANSCRIPTION COACTIVATOR
b-catenin is located in 2 places:
1 - destruction complex - target degradation
2 - adherens junction protein
Regulation of transcription factors - ligand bindinglink b/w environment and transcription through nuclear receptors (nuclear receptors are a type of transcription factors)
Nuclear receptorsreceptors that shuttle to/or already present in the nucleus upon ligand interaction and then regulate transcription by binding to specific DNA sequences; can bind as MONOMERS, dimers, heterodimers
endocrine disrupters affect on nuclear receptorsi.e. acne medications disrupt nuclear receptor signalling -> birth defects
Retinoic acidmetabolite of vitamin A that mediates the functions of vitamin A required for growth and development

LOSS OF RETINOIC ACID
affects multiple developmental processes (retinoic acid binds to RXR and sit on enhancer element of gene, activate co-activator complex and get transcription activation; without RA - get co-repressor complex and repress transcription)
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Question Answer
Lim1 knockouttranscription factor expressed during brain development, without it you get headless mice
MODYaffecting levels of transcription factor results in disease; MODY were identified as genetic determinants of diabetes (they produce transcription factors that bind to and affect expression of insulin)
Mutated MODY genes -> diabetes
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