Regulation of Gene Expression

Basic Conceptions of Gene Expression Regulation

* geneDNARNA (genome) rRNAtRNA* (gene expression)

(cell or tissue specificity)(spatial specificity)

(housekeeping gene)(constitutive gene expression)

(induction) (repression)

(coordinate expression)(coordinate regulation)

Basic Principles of Gene Expression Regulation

DNADNARNA/

(operon)

(consensus sequence) RNA

2 (repressor)RNARNADNA

-7+28RNA-35+20RNADNA

3) (activator)DNARNARNARNA

TATACAATRNA

2) (trans-acting factor)

DNADNA-(dimer)(polymer)

RNA /RNA RNA RNADNA--RNA

Regulation of Gene Expression in Prokaryote

1. RNA2. 3. 4. mRNA----SD5. (1) (2)

1961MonodJacob(lactose operonWatsonCrickDNA1965Jacob and Monod

23 1- 2- 3-

structural geneoperator,Opromoter,P(operon) regulator gene

RNA

(lac operon) CAPCAP(catabolite gene activator portein, CAP)

IPTG(--D-, isopropylthiogalactoside)IPTGIPTG

cAMP-CAPcatabolite gene activator portein) CAPCAP cAMPCAPCAPRNA50 cAMPcAMPCAPlaccatabolic repression

The base sequence of the lac promoter deviates considerably from the consensus sequence of strong promoters, thus being a relatively weak promoter; cAMP-CAP complex is required for optimal expression of the lac operon.

CAP-cAMP binds to a palindromic site near the promoter using two helix-turn-helix motifs and causes DNA bending.Mechanism of allosteric control of CAP. Schematic models of CAP in the 3 structurally characterized states: apo-CAP , CAP-cAMP2, and CAP-cAMP2-DNA . PNAS April 28, 2009 vol. 106 no. 17 69276932Flash

CAPCAP-cAMPcAMPcAMPCAPlac

cAMPcAMPCAP

/ lacCAP1CAP2CAP

cAMP cAMPFlash

RhoRho GCT

mRNAmRNA(autogenous control)

RNA (antisense RNAmRNARNARNAmRNARNAmRNA30SSD(antisense control)

Regulation of Gene Expression in Eukaryote

DNA

(monocistron) mRNA

RNARNARNA pol III IIIRNA

DNADNA:

DNADNA DNA5%DNA

LysH2AH2BH3H4 DNA

DNA 1.DNARNA

(enhancer)DNA (silencer)

DNA(general transcription factors) RNATATA box TFDGC boxSP1 OCT-2Ig

DNA(DNA-binding domain)--(helix-turn-helix)(zinc finger motif)- (leucine zipper)

--(helix-loop-helix, HLH)CAAT

(zinc finger)

12aaC CysH HisGC

SP1 GC 3

-(basic zipper,bzip) 2030DNA Lue, L

mRNARNA13-9 Flash

hnRNAmRNA (ribonucleoprotein, RNP)

eukaryotic initiation factor, eIF

RNA

RNA RNA (small interfering RNA, siRNA)RNA(double-stranded RNAdsRNA)(21-23)RNAsiRNARISC (RNA-induced silencing complex)mRNAmRNApost-transcriptional gene silencing,PTGS)siRNARNA(RNA interferenceRNAi)

RNAi Dicer

RISC

Dicer: RNasesiRNA: small interfering RNA 21~23ntRISCRNA(RNA-induced silencing complex)siRNAATPdsRNAmRNA

RNA (RNAi)RNAi20012002RNAiScience2006(Andrew Fire) (Craig Mello)RNA2006

EPO5522RNA RNAi

*DNA*DNA*DNA

siRNA, RNAiDNA---