Regulation of Gene Expression by Eukaryotes

1. Regulation of Gene Expression by Eukaryotes

2. Gene expression in eukaryotic cells • Typical human cell: only 20% of genes expressed at any given time • Different cell types (with identical genomes) turn on different genes to carry out different functions • Differences between cell types is due to differential gene expression

3. Eukaryotic gene expression regulated at different stages

4. First stage: At the DNA level Chromatin Structure: • Tightly bound DNA  less accessible for transcription

5. First stage: At the DNA level • DNA methylation: • Methyl groups are added to the DNA molecule • Changes the activity of a DNA segment without changing the sequence • When located in a gene promoter, it typically acts to repress gene transcription

6. First stage: At the DNA level • Histone acetylation: • acetyl groups added to histones; • Chromatin loosened;  transcription

7. Epigenetic Inheritance • Epigenome: • All of the chemical compounds that have been added to the entirety of one’s DNA • Not part of the DNA sequence • Can be inherited through the generations

8. Genetic Science Learning Center Video: The Epigenome at a Glance

9. Genetic Science Learning Center Video: The Epigenetics of Identical Twins

10. Second stage: At the transcription level Transcription Initiation: • Specific transcription factors (activators or repressors) bind to control elements (enhancer region) • Activators: increase transcription • Repressors: decrease transcription

11. Transcription Initiation Complex • TATA box: attracts transcription factors • Transcription factors: attracts RNA Polymerase • Enhancer: A DNA region that can be bound by activators/repressor to increase/decrease transcription

12. Cell type-specific transcription • A particular combination of control elements can activate transcription only when the appropriate activator proteins are present

13. Third stage: At the post transcriptional level • Alternate splicing of RNA • Makes it possible for a single gene to encode several polypeptide • Initiation of translation • Can be blocked by regulatory proteins that binds to sequences or structures of the mRNA • After translation - Various types of protein processing, including cleavage and chemical modification

14. Alternate Splicing • A prominent mechanism to generate protein diversity • Takes place within the nucleus either during or immediately after transcription • Particular exons of a gene may be included within or excluded from the final mRNA

15. Third stage: At the post transcriptional level Regulation of mRNA: • Micro RNA (miRNA): Inhibit translation of mRNA • Small interfering RNA (siRNA): Cleave mRNA

16. Prokaryotic Vs. Eukaryotic • Prokaryotic • Transcription in cytoplasm • Uses operon as functional units • Regulatory gene makes repressor • DNA mRNA Protein • One mRNA codes for several proteins (Polycistronic) • Eukaryotic • Transcription in nucleus • Uses transcription factors • Regulatory gene are bound by various transcription factors • DNA PremRNA mRNA Protein • One mRNA codes for one protein