BIOL 1107 - Regulation of Gene Expression

How do cells regulate metabolic pathways?

Cells can regulate metabolic pathways via feedback inhibition of enzyme activity or via the production of enzymes (transcription of the corresponding genes)

Operon structure and function

-a cluster of functionally related genes (that collaborate within the same metabolic pathway) can be controlled by a single switch on/off system

• a DNA sequence called the operator is located near the promoter

• an operon is the whole stretch of DNA that includes the promoter, the operator, and the genes that they control

Hoe can an operator be switched off

operons can be switched off by a repressor that binds to the operator, preventing the RNA polymerase to attach (ex, no more transcription of the controlled genes)

Repressor function

-the repressor can be active or inactive

-it can bind with another molecule called the corepressor, which is usually related to the metabolic pathway controlled by the operon

Repressible operon

-the operon is usually “on.” the repressor is inactive (for example, the tryptophan operon). Tryptophan is synthesized by default

-when there is too much product (tryptophan), it acts as a corepressor and attaches to the repressor that becomes active

-the repressor then attaches to the operator and switches off the operon

-repressible operons are usually related to anabolic pathways

Inducible operon

-the operon is usually “off.” the repressor is active and attached to the operator (for example, lactose operon)

-when lactose is present, it binds to the repressor that becomes inactive. It acts as an inducer

-the operon is switched on and the enzymes that break lactose are produced

-inducible operons are usually related to catabolic pathways

Gene expression

-essential to cell specialization in pluricellular organisms. the control often implies cell communication

-almost all cells of an organism contain the same genes, but only a few specific genes are expressed in a given cell

-regulation occurs at many stages, but mostly at gene transcription

Chromatin regulation

-genes located in compact heterochromatin are usually not expressed

-genes located in euchromatin are more likely to be expressed, but the position of the nucleosome may play a role

-DNA methylation (addition of methyl group to DNA) is associated to low transcription

Control elements

-genes can have control sequences located close (proximal control elements) or far (enhancer sequences) from the promoter

-these sequences are recognized by transcription factors. These factors facilitate the attachment of the RNA polymerase to the promoter

• by default, the RNA polymerase very often fails to attach

• once the transcription factors are present, the polymerase attaches much more often, which increases transcription frequency

-activation sequences and transcription control should match to be efficient. Depending on the cell, only some transcription factors are present. therefore, only some specific genes are enhanced

-eukaryotic genes are not organized in operon, by related genes usually have the same control sequences and react to the same control molecules

Post-transcriptional regulation

-alternative splicing

-mRNA can stay a long or a short time in the cytoplasm, and therefore be translated many or just a few times

Alternative splicing

transcribed RNA can be processed in different ways. Introns can be removed differently, and some exons can be treated as introns. From the same transcribed RNA, it is possible to have a few different mRNA (and a few different proteins)

Post-translational regulation

-newly synthesized proteins may undergo processing (addition of polysaccharides, cleavage)

-proteins can be marked for degradation

What does a small fraction of DNA code for?

proteins, rRNAs, and tRNAs

ncRNAs

-some of the genome (non-coding) is transcribed into non-coding RNAs (ncRNAs)

• Micro-RNAs

• Small interfering RNAs

Micro-RNAs

(miRNAs) are small sequences that bind with some sequences of mRNA and either cause degradation of this mRNA or block its translation

Small interfering RNAs

(siRNAs) are similar to miRNAs

Embryonic development - cell types

during embryonic development, a fertilized egg gives rise to many different cell types

What drives the developmental program

the developmental program is driven by gene expression

Role of maternal cells

material placed in egg by maternal cells sets up the program for gene expression that is passed to daughter cells

Cytoplasmic determinants

maternal substances in the egg that influence early development (cell division splits these determinants non-evenly, which influences their future development)

Cell…

also communicate with other cells. They will undergo determination that irreversibly determines their future determination

Pattern formation

the development of a spatial organization of tissues or organs. It is well known in the fruit fly development

Patter formation in fruit flies

-begins with establishment of major polarity axes (antero-posterior, dorsal-ventral, left-right)

-cells’ development is controlled by positional information (via molevules)

-it starts with determinant in the unfertilized egg

-cell division will create specific areas (segments) that will express some specific factors

-in later stages, homeotic genes control patterns formation

-similar systems exist in mammals

Macroevolution

-creation of novel body shapes

-could result from mutations of development genes

Cancer is…

due to a default in gene regulation for cell division

Proto-oncogenes

-genes that code for proteins that stimulate normal growth and cell division

• if they have a mutation, they can become oncogenes (unregulated)

• it can result from an increase of gene activity or the protein activity (please figure out what the heck this means)

Tumor-suppressor genes…

normally inhibit cell division

Proto-oncogene ras

-a G-protein that relays the signal of growth factors received by a receptor

• if mutated, the G-protein remains active, and the signal is transmitted even without growth factors

Tumor-suppressor p53

-controls damage in cell DNA, can inhibit the cell cycle, can trigger genes involved in DNA repair, and can even trigger apoptosis (cell suicide) if the damages cannot be repaired

• if mutated, p53 does not prevent cell division

Cancer results from…

a series of mutations that affect proto-oncogenes (that become oncogenes) and tumor-suppressors (that are not active)

Genetic predispositions exist…

if people inherit oncogenes or mutated tumor-suppressors

Viruses…

that integrate their DNA with cell DNA can interfere with normal gene regulation