OBJ - Eukaryotic Gene Regulation Flashcards
Describe the organization of a eukaryotic promoter.
“Basic” view: (but actually VERY COMPLEX - Kilobases long)
Distal Promoter Proximal Control Elements - GC Box (-100) - CAAT Box (-80) Core Promoter - Transcriptional Start Site (TSS) - TATA Box (-25) - Binding sites for RNA Polymerases I, II & III
Identify the major post-translational modifications of histone proteins.
Histidine, Arginine, Lysine (HAL) Tails = variety of PostTranslational Modifications
2 Major = Acetylation & Methylation
Acetylation - removes + charge on histone
heterochromatin -> euchromatin because no longer + charge to all negative charges that repel each other & open up
Methylation - no change in charge
- can observe, but cannot predict
- spatial presentation to factors
- both DNA & histones can be methylated by cytosines
DNA
- Methylating DNA -> OFF
- Unmethylated DNA -> ON
- GOAL: Creating a scaffold to attract other proteins (Bromo & Chromo domains)
- attract to self for binding
- attract for enzymatic activity for nearby histones
Other Posttransaltional
- Ubiquination
- SUMOylation
- Phosphorylation (AA with OH groups- Serine Threonine)
NOT simple & SUPER complex!!!
Describe the basic structure of a nuclear receptor.
Nuclear Receptor Superfamily: Steroids & Thyroid hormones
2 Fingers that contain Zinc (Proximal & Distal Boxes)
Bind to DNA as a Dimer in recognition sequence
Differences in recognition sequence - in zinc fingers - total of 3 Amino Acids that specify receptor
Ligand Binding Domain
Helix 12 -> depending on steroid hormone - affects angle/position Helix 12 flips to
-> changes scaffold & recruitment of cofactors
Work to express/repress certain genes; controlling development, homeostasis & metabolism of the cell/organism
Ex: Testicular Feminization -> comes full circle
Explain the sequence of steps by which steroid hormones increase/decrease the rate of transcription of hormonally responsive genes.
Hormone receptor binds to GRE; changes scaffold & is recognized by complex of transcription factors that modify chromatin structure
Sequential modification of chromatin structure recruits RNA Polymerases to promoter
RNA Polymerase + mediator binds to transcription, co factors & ligand (Helix 12) that causes conformational change
- > Transcription gets turned ON or OFF (up regulated or down regulated) depending on effect wanted
- > To keep gene OFF - recruit repressor complex
Eukaryotic Gene Expression
Needs to be regulated:
- TEMPORALLY (at certain times & not at others)
- SPATIALLY (only certain tissues)
Euchromatin
DNA that is accessible/open/unwound & being duplicated
“Turned ON”
Light on LM
Heterochromatin
DNA not accessible because so tightly wound
- “Turned OFF”
DARK on LM
Compacted chromatin by electrostatic binding between:
+ charge histone tail
- charged DNA
Bromo domain
Recognizes acetylated lysines
Chromo domain
Recognizes methylated histones
