Topic 5 - Regulation of Gene Expression

Operon

DNA segment

Includes the operator, the promoter and a group of functionally genes

Repressor

Switches off the operon

prevents gene expression by binding to the operator and blocking RNA polymerase binding

Operons OFF (active repressors)

Negative Regulation

Repressive Operons

Active

Inactivated by high levels of co-repressors which activate the repressor (i.e trp operon)

Inducible Operons

Inactive

Activated by chemical signals which inactivate the repressor

(i.e lac operon)

Present Tryptophan

What happens to the repressor?

What happens to the operon?

Active Repressor

Inactive Operon

Absent Tryptophan

What happens to the repressor?

What happens to the operon?

Inactive Repressor

Active Operon

High levels of Tryptophan

What happens to the trp operon?

Turned off trp operon

Absent Lactose

What happens to the repressor?

What happens to the operon?

Active Repressor

Inactive Operon

Present Allolactose

What happens to the repressor?

What happens to the operon?

Inactive Repressor

Active Operon

Present Lactose and Little Glucose

cAMP levels?

CAP?

High cAMP levels

Active CAP and increased affinity of RNA polymerase

Present Lactose and Glucose

Low cAMP levels

Inactive CAP and decreases affinity of RNA polymerase

Epigenetic Inheritance

The inheritance of traits transmitted by mechanisms independent of nucleotide sequence changes

Nucleosome

Structural unit of DNA packaging in eukaryotes

DNA wrapped around histones

Histone Acetylation

Addition of -COCH3

Negatively Charged

Activation of chromatin → euchromatin

Histone Deacetylation

Removal of -COCH3

Positively Charged

Inactivation of Transcription → heterochromatin

Histone Phosphorylation

Addition of a phosphate group

Chromatin decompensation

Activation of gene expression → euchromatin

What does DNA methylation reduce?

Transcription

Genomic Imprinting

Silencing of either the maternal or paternal alleles for certain genes

Activators

Bind to an enhancer and stimulate specific gene transcription

Repressors

Inhibit transcription and expression of a particular gene

Post-Translational Modifications

1. Polypeptide cleavage

2. Protein folding

3. Subunit assembly

4. Chemical modifications

1,2,3 → in the RER

4 → in the RER but mostly in the Golgi

Proteasome

Protein degradation

That’s when Ubiquitin is on the protein

miRNAs

Degrade the mRNA or block its translation

siRNAs

Cause RNA interference → inhibition of gene expression by RNA molecules

RNA degradation

What does the Epstein-Barr virus cause?

Burkitt’s lymphoma and Nasopharyngeal carcinoma

What do Human Papilloma viruses cause?

Cervical carcinoma and warts

What does the Hep B virus cause?

Hepatocellular carcinoma

HTLV-I

Adult T-cell leukemia lymphoma

Acutely Transforming Oncogenic Retroviruses

Avian Erythroblastosis Virus

Avian Meylocytomatosis Virus

They cause tumors by transduction of the viral oncogene

Slowly Transforming Oncogenic Retroviruses

Mouse mammary Tumor virous (MMTV)

Avian Leukosis (ALV)

Causes tumors by insertional mutagenesis

Oncogenes

Trigger the molecular events that lead to cancer

→ INDUCE UNCONTROLLED CELL DIVISION

Tumor suppressor genes

Their protein inhibits sex selection

→ INHIBIT UNCONTROLLED CELL DIVISION

Proto-oncogenes

Responsible for normal cell growth and division

What does the inactivation of tumor suppressor genes lead to?

Leads to carcinogenesis

Role of tumor suppressor proteins

Inhibit cell cycle and induce apoptosis

What is the tumor suppressor gene of the oncogene HER-2?

p53

What is the tumor suppressor gene of the oncogene Ras?

BRCA-1 and BRCA-2