Eukaryotic Gene Regulation

What is genomic equivalency?

All the cells in the embryo have the same genome

For reptiles, what is a very notable example of gene regulation in response to environmental cues?

Temperature dependent sex determination

In __ temps, turtles develop into males, and in __ temps, turtles develop into females

High (32C), low (26C)

Describe the mechanism for temperature dependent sex determination in turtles

1. In hot temps, the Ca⁺² channel in the gonadal precursor cells are open, and allow for an influx of calcium. In low temps, the channels are closed.

2. The calcium influx in hot results in the TF STAT3 being phosphorylated. In cold, it is unphosphorylated.

3. When phosphorylated, STAT3 is a transcriptional repressor for the gene Kdmbb → the turtle will be a male. When unphosphorylated, Kdmbb can be transcribed, and the turtle will be a female.

What are the 6 levels of gene regulation?

1. Epigenetics: chromosome structure. Related to packaging. Histone modifications, DNA methylation, RNA molecules.

2. Transcription initiation: cis elements, regulatory promoters, cell-type specific transcription factors, activators and repressors (trans elements)

3. RNA Processing: Alternative splicing, 3’ PolyA tail, 5’ cap

4. Nuclear Export

5. RNA Stability

6. Post Translational Modifications

What are the two key aspects of the core promoter?

TATA Box

-35 consensus seq (GC rich)

The __ promoter is required for the activation of every gene

core

What is different about the regulatory promoter versus core promoter?

Regulatory: Gene specific, contains info for cell-type specific expression, binding sites for enhancers and silencers

Core: Required for the activation of every gene

RECALL, what are the factors of the general transcription apparatus?

1. TFIIs

2. TATA Binding Protein (TATA Binding Protein)

3. RNA Pol II

What is the mediator complex?

Bridge between cell-type specific factors and the general transcription apparatus, forming a sort of loop structure

What is enhancer modularity?

The concept that gene regulation is controlled by separated, discrete DNA sequences (enhancers) that function independently to drive gene expression in certain contexts

__ ___ transcription factors initiate cell fate programs

Master Regulatory

Name 4 examples of master regulatory TFs

1. Oct3/4

2. c-Myc

3. Sox2

4. Klf4

What TF is required for pancreas precursor identity?

Cell fate