• Developmental Regulation
• Cell-specific Regulation

Development involves co-ordination of gene expression.
Mutants in Drosophila melanogaster (fruit fly) have been used to study development

eg. Antennapedia - mutation causes leg to grow instead of antenna.

• Example of homeostasis - one body part looks like another
• Antp gene contains a homeobox sequence:


• Encodes a homeodomain protein
• Homeodomain proteins are TRANSCRIPTION FACTORS
• their expression is regulated by other transcription factors
• eg. Antp is positively  regulated by itself,

 

 



• and is repressed by

Ubx

Drosophila develops in segments. Each segment in the embryo gives rise to a different parts

Sequential expression of genes, controlled by transcription factors which bind to enhancers upstream of the promoters of controlled genes.
A cascade of regulation, each step leads to greater specialization.

• Maternal factors -present in egg eg Bicoid. Switches on expression of Hunchback
• Gap Factors - eg Hunchback, regulates expression of other Gap factors eg Krupple, knirp
• Pair-rule Factors - eg Ftz, Eve, Prd. Regualated by Bicoid in combination with Gap factors
• Segment Polarity Factors - eg engrailed. Leads to development of parasegments
• Selector Factors - eg Antp and Ubx. Controlled by Gap factors. Development  of structures eg legs. Regulate expression of structural components etc.

 

 
 
 
 
 

• How do cells achieve specificity - ie differences between cell types?
• B-Cells express immunoglobulin Heavy and k Light chains
• Regulatory Sequences upstream and downstream are responsible:


• Octamer sequence
• NFkB binding site

 
• Regulatory Proteins:
• Oct-2  is expressed in B-Cells, is a homeodomain protein, binds to DNA
• OCA-B  is expressed in B-cells, doesn’t bind DNA. Binds Oct-2 to regulate transcription.
• NFkB is expressed in many cells.

 

 
 
 

Phosphorylation causes dissociation of NFkB from IkB,

NFkB can then go to the nucleus to regulate transcription.
 
 

Complex Regulation:

Reading- Lodish Chapter 14 p538-
Instant Notes in Mol Biol - N2

Questions:
1. Explain how transcription factors are important in development
2. Give an example of how cell-specific transcriptional regulation is achieved

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