Regulation of Gene Expression pg 701-30 ; p 741-21
Permitting or inhibiting transcription - gene "off" or "on"
Catabolic vs anabolic pathways
Prokaryotes - adaptive enzyme synthesis
Operon model - Jacob and Monod
Single regulatory unit
Includes - structural genes for pathway and regulatory genes
Polycistronic mRNA
Two types of negative control - Repressor protein turns off transcription
Repressor protein
Binds to operator which prevents RNA polymerase from binding to promotor
Regulatory gene outside operon codes for repressor
Repressor is an allosteric protein
Inducible operon - default condition is off, must be turned on
Common to catabolic pathways
Example: lac operon [Fig 21-4]
Regulator gene - lacl (outside operon) - codes for repressor protein
Operator and Promoter
Structural genes for Beta-gal, permease, transacetylase
Effector - allolactose - inactivates repressor
Presence of lactose induces transcription - gene turned on
Repressible operon - must be turned off
Common to anabolic pathways
Example: Trp operon [Fig 21- 6]
Operator, Promoter and Leader seq
Structural genes for enzymes in tryp pathway
Regulator gene - trpR (outside operon) - codes for repressor protein
Effector - corepressor, tryptophan (product) - activates repressor
Also (Ch 19) sigma factors
-------------
Eukaryotes - multiple levels of control [Fig 21-11]
the single cistron model
Accessibility of genes
Nucleus
Generalized repression of chromosomal regions - heterochromatin
nucleosome (Ch 16)
Transcriptional Control - most often at initiation
Different RNA polymerases
Common organization of eukar. gene [Fig 21-21]
Basal transcription factors include a common DNA binding protein
(TFIID)and other proteins forming complex at core promotor permitting
low levels of transcription
Proximal regulatory elements (part of DNA)upstream - sites for interaction
with other regulatory transcription factors [prots]
Combinatorial model of gene regulation [Fig 21-23, 24]
Regulatory sequences can be anywhere - not like prokaryotes
Regulatory proteins [activators] bind to enhancer region of DNA -
enhanceosome
DNA bends to position enhanceosome near core promotor
Reg prots of enhcanceosome bind to coactivators on TFIID facilitating
its binding to the promotor
Other TFs and RNA polymerase form complex and transcription ensues
Silencers are known but poorly understood
Post-transcriptional regulation
Splicing Ch 20, etc
Functional conformation
mRNA half life[Fig 21-34]
Post-translational regulation
Protein degradation by proteasome [Fig 21-36]