Lecture III: Molecular Logic of Asymmetry
Zhang Yi,
National Institute of Biological Sciences, 20080628

Cellular Anatomy

Mitosis V.S Meiosis a a
α
α

Mating Type Switch

Mating Type Specific Gene
• MATa gene expression
– a1 mRNA from MATa locus
– Other a-specific gene expression is default
• Driven by MCM1 homodimer
• MAT  gene expression
– 
1,

2 mRNA from MAT

– 
1 and

2 function
• Repress a-specific genes
– 
2/MCM1 heterodimer
• Stimulate 
-specific genes
– 
1/MCM1 heterodimer

Mating Type Specific Gene Expression

Mating Type Switch Mechanism:
HO

Mating Type Switch Mechanism: hetero-sequence switch

Recombination Enhancer Sequence

Sequence-Specific RE Effects

RE Sequence Shows MatAlpha2
Binding Site

RE Mutants Render Chromatin
Structural Change wt
… mt
…

A Mcm1p Binding Site in RE is
Necessary for RE Function

MatAlpha2 Interaction with Tup1/Ssn6 is Essential for
Haploid/a-specific Gene Repression

Tup1/Ssn6 Complex is Global Transcription
Suppressor Associated with HDACs

A Model Summarizing Mcm1p-Mediated
Chromosomal Effects on RE and Other Loci

S.Pombe
Evolution of the Molecular Logic of
Mating Type in Fungi

Maternal Effect on Mating Type Switch
???

HO Promoter Dissection

HO Expression Depends on
Swi/Snf Complex: LOF and GOF

Ash1p Represses Mating Type Switch in
Daughter Cell by Inhibiting HO Expression

Ash1p and Swi/Snf Show Reciprocal
Effects on Mating Type Switch

Ash1p Localization Dependence:
Genetic Screen
Screen for mother cells who do NOT express HO (promoter is inhibited) as a consequence of any genetic defect

She Genes are Necessary for HO Expression

She1p/5p are Cytoskeletal Proteins, and Some
She Genes are Localized to Daughter Cells
Interdependence of She genes on localization

FISH
Genetics
LOF
Actin-dependent Ash1 mRNA
Localization into Daughter Cell
Pharmacology
LOF
Genetics
GOF

She genes and Ash1 mRNP transport

Visualizing mRNA Transport

Local Translation

Local Translation Regulation is as
Essential as Localization

Protein Level in Temporal Context
Degredation for old alpha2 as well as HO etc

Protein Dynamics not Limited to
Ash1 mRNA Transportation