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PMID:23417560

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Citation

Stevenson, JS and Liu, H (2013) Nucleosome Assembly Factors CAF-1 and HIR Modulate Epigenetic Switching Frequencies in an H3K56 Acetylation-Associated Manner in Candida albicans. Eukaryotic Cell 12:591-603

Abstract

CAF-1 and HIR are highly conserved histone chaperone protein complexes that function in the assembly of nucleosomes onto chromatin. CAF-1 is characterized as having replication-coupled nucleosome activity, whereas the HIR complex can assemble nucleosomes independent of replication. Histone H3K56 acetylation, controlled by the acetyltransferase Rtt109 and deacetylase Hst3, also plays a significant role in nucleosome assembly. In this study, we generated a set of deletion mutants to genetically characterize pathway-specific and overlapping functions of CAF-1 and HIR in C. albicans. Their roles in epigenetic maintenance of cell type were examined by using the white-opaque switching system in C. albicans. We show that CAF-1 and HIR play conserved roles in UV radiation recovery, repression of histone gene expression, correct chromosome segregation, and stress responses. Unique to C. albicans, the cac2Δ/Δ mutant shows increased sensitivity to the Hst3 inhibitor nicotinamide, while the rtt109Δ/Δ cac2Δ/Δ and hir1Δ/Δ cac2Δ/Δ mutants are resistant to nicotinamide. CAF-1 plays a major role in maintaining cell types, as the cac2Δ/Δ mutant exhibited increased switching frequencies in both directions and switched at a high frequency to opaque in response to nicotinamide. Like the rtt109Δ/Δ mutant, the hir1Δ/Δ cac2Δ/Δ double mutant is defective in maintaining the opaque cell fate and blocks nicotinamide-induced opaque formation, and the defects are suppressed by ectopic expression of the master white-opaque regulator Wor1. Our data suggest an overlapping function of CAF-1 and HIR in epigenetic regulation of cell fate determination in an H3K56 acetylation-associated manner.

Links

PubMed Online version:10.1128/EC.00334-12

Keywords


Significance

Annotations

Gene product Qualifier GO Term Evidence Code with/from Aspect Extension Notes Status

CANAL:HIR1

involved_in

GO:0007059: chromosome segregation

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

CANAL:HIR1

GO:0007059: chromosome segregation

ECO:0000315:

P

Figure 2B shows that cells with a mutant HIR1 gene produced more 4N cells than the wild type. Figure 2C shows these 4N cells were due to abnormal nuclear localization, or an abnormality in chromosome segregation. This indicates that HIR1 is needed for proper chromosome segregation.

complete
CACAO 7937

CANAL:HIR1

part_of

GO:0000417: HIR complex

ECO:0000315: mutant phenotype evidence used in manual assertion

C

Seeded From UniProt

complete

CANAL:HIR1

involved_in

GO:0000070: mitotic sister chromatid segregation

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

CANAL:A0A1D8PNS7

GO:0007059: chromosome segregation

ECO:0000315:

P

Figure 2B shows that cells with a mutant CAC2 gene produced more 4N cells than the wild type. Figure 2C shows these 4N cells were due to abnormal nuclear localization, or an abnormality in chromosome segregation. This indicates that CAC2 is needed for proper chromosome segregation.

complete
CACAO 7942

CANAL:A0A1D8PNS7

involved_in

GO:0000070: mitotic sister chromatid segregation

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

CANAL:A0A1D8PNS7

part_of

GO:0033186: CAF-1 complex

ECO:0000315: mutant phenotype evidence used in manual assertion

C

Seeded From UniProt

complete

CANAL:A0A1D8PNS7

involved_in

GO:0007059: chromosome segregation

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete


See also

References

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