6.gene expression

Biochemistry Chen Yonggang Zhejiang University Schools of Medicine

Regulation of Gene Expression: Putting information to work

Information encoded in DNA is of no use unless it is expressed ,[object Object],[object Object],[object Object],[object Object]

Bacteria are simpler than eucaryotic cells but have similar processes ,[object Object],[object Object],[object Object]

Gene expression systems be understood by studying two models ,[object Object],[object Object],[object Object],[object Object],[object Object],[object Object]

Life processes are controlled by enzymes, gene products ,[object Object],[object Object],[object Object]

The easiest bacterium to study is E. coli ,[object Object],[object Object],[object Object],[object Object]

The energy for growth and function comes from food ,[object Object],[object Object],[object Object]

E. coli does not normally express the enzymes needed to use lactose ,[object Object],[object Object]

The lac operon, an inducible operon McKee 18.28

The lac operon contains regulatory and structural genes ,[object Object],[object Object],[object Object],[object Object],[object Object]

To use lactose, 3 structural genes are required at the same time ,[object Object],[object Object],[object Object]

The LacI gene encodes a control protein, a repressor ,[object Object],[object Object]

The repressor/operator interferes with RNA polymerase binding ,[object Object],[object Object],[object Object]

When lactose is available, the Lac operon is activated ,[object Object],[object Object],[object Object],[object Object]

Induction of the lac operon McKee 18.29

The repressor/inducer complex does not bind to the operator ,[object Object],[object Object]

Control of a catabolic operon Devlin 8-3

Mutations in genes affect operon expression ,[object Object],[object Object]

Glucose is a breakdown product of lactose and the preferred fuel ,[object Object],[object Object],[object Object],[object Object],[object Object],[object Object]

CAP encodes a protein, Catabolite Activator Protein ,[object Object],[object Object],[object Object],[object Object]

cAMP-CAP exerts positive control, enhancing transcription of the operon Devlin 8-6

The Lac operon is an inducible system ,[object Object],[object Object]

Anabolic, biosynthetic operons are regulated differently ,[object Object],[object Object],[object Object],[object Object]

The Trp operon is similar to the Lac operon in structure ,[object Object],[object Object],[object Object],[object Object],[object Object]

Trp R , not associated with the operon constituitvely synthesizes a repressor ,[object Object],[object Object],[object Object],[object Object]

The trp operon is repressible Devlin 8-7

In addition to gene regulation, the pathway is regulated by enzymes ,[object Object],[object Object],[object Object]

Such enzymes, called Flux-Determining Enzymes are regulated ,[object Object],[object Object],[object Object]

Tryptophan synthesis is controlled by gene expression and enzyme activity ,[object Object],[object Object],[object Object]

Eucaryotic Regulation ,[object Object],[object Object],[object Object]

Scientists used to believe that based on evolution, simpler is better ,[object Object],[object Object],[object Object],[object Object]

Eucaryotic genes are organized in logical arrays ,[object Object],[object Object],[object Object],[object Object]

Gene clustering may be related to expression ,[object Object],[object Object]

Gene expression in eucaryotes occurs from chromatin, not DNA ,[object Object],[object Object],[object Object],[object Object]

The structure of transcriptionally active chromatin is unique ,[object Object],[object Object],[object Object],[object Object]

The DNA of active genes may be altered either in structure or access ,[object Object],[object Object]

Gene expression is primarily controlled by transcription ,[object Object],[object Object],[object Object],[object Object]

Eucaryotic RNA polymerases cannot act alone ,[object Object],[object Object],[object Object]

DNA access can be modified ,[object Object],[object Object]

Methylation of cytosines blocks access to TFs Devlin 8-20

Activation of transcription depends on forming an initiation complex ,[object Object],[object Object],[object Object]

In general, all transcription factors have two domains ,[object Object],[object Object],[object Object],[object Object]

There are many general TFs required for transcription ,[object Object],[object Object],[object Object]

The TATA box anchors the initation complex Devlin 8-22

While binding to the TATA box is essential, it is not sufficient ,[object Object],[object Object],[object Object],[object Object],[object Object]

Eucaryotic genes can have multiple promoters ,[object Object],[object Object],[object Object]

Four common DNA binding motifs are used in TFs ,[object Object],[object Object],[object Object],[object Object]

Transcription factor DNA binding domains are sequence specific ,[object Object],[object Object],[object Object],[object Object],[object Object]

Helix-turn-helix proteins are found in both procaryotes and eucaryotes ,[object Object],[object Object],[object Object]

HTH domains bind in the major groove of DNA Devlin 8-24

Each domain has a specific role ,[object Object],[object Object],[object Object]

Specific binding occurs in the major groove Devlin 9-19,20

The Zinc finger motif binds specific sequences in the DNA ,[object Object],[object Object],[object Object]

Zinc fingers can wrap in the major groove of DNA Devlin 9-22

Zinc fingers mediate hydrogen bonding ,[object Object],[object Object]

Leucine zippers use dimeric helical molecules to bind DNA ,[object Object],[object Object],[object Object],[object Object]

Leucine zippers are common motifs Devlin 8-26,9-25

The Helix-Loop-Helix is a variation on the HTH motif ,[object Object],[object Object]

HLH proteins bind to DNA sequences Devlin 8-27

Transcription is controlled through common mechanisms ,[object Object],[object Object],[object Object]

Initiation of transcription ,[object Object],[object Object],[object Object],[object Object]

Transcription is precisely regulated to meet the needs of the cell Devlin 8-30

Questions for you to think about ,[object Object],[object Object],[object Object],[object Object]

6.gene expression

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