Limits...
Hyphal development in Candida albicans requires two temporally linked changes in promoter chromatin for initiation and maintenance.

Lu Y, Su C, Wang A, Liu H - PLoS Biol. (2011)

Bottom Line: Although many regulators have been found involved in hyphal development, the mechanisms of regulating hyphal development and plasticity of dimorphism remain unclear.Maintenance requires promoter recruitment of Hda1 histone deacetylase under reduced Tor1 (target of rapamycin) signaling.Such temporally linked regulation of promoter chromatin by different signaling pathways provides a unique mechanism for integrating multiple signals during development and cell fate specification.

View Article: PubMed Central - PubMed

Affiliation: Department of Biological Chemistry, University of California, Irvine, California, United States of America.

ABSTRACT
Phenotypic plasticity is common in development. For Candida albicans, the most common cause of invasive fungal infections in humans, morphological plasticity is its defining feature and is critical for its pathogenesis. Unlike other fungal pathogens that exist primarily in either yeast or hyphal forms, C. albicans is able to switch reversibly between yeast and hyphal growth forms in response to environmental cues. Although many regulators have been found involved in hyphal development, the mechanisms of regulating hyphal development and plasticity of dimorphism remain unclear. Here we show that hyphal development involves two sequential regulations of the promoter chromatin of hypha-specific genes. Initiation requires a rapid but temporary disappearance of the Nrg1 transcriptional repressor of hyphal morphogenesis via activation of the cAMP-PKA pathway. Maintenance requires promoter recruitment of Hda1 histone deacetylase under reduced Tor1 (target of rapamycin) signaling. Hda1 deacetylates a subunit of the NuA4 histone acetyltransferase module, leading to eviction of the NuA4 acetyltransferase module and blockage of Nrg1 access to promoters of hypha-specific genes. Promoter recruitment of Hda1 for hyphal maintenance happens only during the period when Nrg1 is gone. The sequential regulation of hyphal development by the activation of the cAMP-PKA pathway and reduced Tor1 signaling provides a molecular mechanism for plasticity of dimorphism and how C. albicans adapts to the varied host environments in pathogenesis. Such temporally linked regulation of promoter chromatin by different signaling pathways provides a unique mechanism for integrating multiple signals during development and cell fate specification.

Show MeSH

Related in: MedlinePlus

yng2K175R mutation suppresses the deficiency of hda1/hda1 in sustained expression of hypha-specific genes.Morphology (A) and Northern analysis (B) of wild type and hda1/hda1 yng2/yng2 transformed with YNG2 or yng2K175R during hyphal induction as in Figure 3. Northern analysis was carried out using 12.5 µg RNA and probes to the indicated filament-specific transcripts. The ACT1 transcript is included as a loading control. (C). Kinetics of Yng2-Myc and Yng2-Myc-K175R promoter binding in hda1/hda1 mutants by ChIP with anti-Myc. Data on ALS3 and ECE1 for (C) are in Figure S5. The ChIP data show the average of three independent qPCR experiments with error bars representing the SEM.
© Copyright Policy
Related In: Results  -  Collection


getmorefigures.php?uid=PMC3139633&req=5

pbio-1001105-g005: yng2K175R mutation suppresses the deficiency of hda1/hda1 in sustained expression of hypha-specific genes.Morphology (A) and Northern analysis (B) of wild type and hda1/hda1 yng2/yng2 transformed with YNG2 or yng2K175R during hyphal induction as in Figure 3. Northern analysis was carried out using 12.5 µg RNA and probes to the indicated filament-specific transcripts. The ACT1 transcript is included as a loading control. (C). Kinetics of Yng2-Myc and Yng2-Myc-K175R promoter binding in hda1/hda1 mutants by ChIP with anti-Myc. Data on ALS3 and ECE1 for (C) are in Figure S5. The ChIP data show the average of three independent qPCR experiments with error bars representing the SEM.

Mentions: If serum-induced Hda1 promoter association leads to Yng2 deacetylation and degradation, the level of promoter-associated Yng2 is expected to decrease during hyphal induction. Indeed, a time course ChIP of Yng2-Myc showed that Yng2 level decreased after 30 min of hyphal induction (Figures 4F and S4B). The level of promoter-associated Yng2K175R showed a similar decrease, whereas the levels of Yng2-Myc in the hda1 mutant and Yng2K175Q-Myc stayed unchanged (Figures 4F, 5C, and S4C). The level of Esa1, the enzymatic subunit of NuA4, showed a similar decrease at the promoters during hyphal induction (unpublished data).


Hyphal development in Candida albicans requires two temporally linked changes in promoter chromatin for initiation and maintenance.

Lu Y, Su C, Wang A, Liu H - PLoS Biol. (2011)

yng2K175R mutation suppresses the deficiency of hda1/hda1 in sustained expression of hypha-specific genes.Morphology (A) and Northern analysis (B) of wild type and hda1/hda1 yng2/yng2 transformed with YNG2 or yng2K175R during hyphal induction as in Figure 3. Northern analysis was carried out using 12.5 µg RNA and probes to the indicated filament-specific transcripts. The ACT1 transcript is included as a loading control. (C). Kinetics of Yng2-Myc and Yng2-Myc-K175R promoter binding in hda1/hda1 mutants by ChIP with anti-Myc. Data on ALS3 and ECE1 for (C) are in Figure S5. The ChIP data show the average of three independent qPCR experiments with error bars representing the SEM.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3139633&req=5

pbio-1001105-g005: yng2K175R mutation suppresses the deficiency of hda1/hda1 in sustained expression of hypha-specific genes.Morphology (A) and Northern analysis (B) of wild type and hda1/hda1 yng2/yng2 transformed with YNG2 or yng2K175R during hyphal induction as in Figure 3. Northern analysis was carried out using 12.5 µg RNA and probes to the indicated filament-specific transcripts. The ACT1 transcript is included as a loading control. (C). Kinetics of Yng2-Myc and Yng2-Myc-K175R promoter binding in hda1/hda1 mutants by ChIP with anti-Myc. Data on ALS3 and ECE1 for (C) are in Figure S5. The ChIP data show the average of three independent qPCR experiments with error bars representing the SEM.
Mentions: If serum-induced Hda1 promoter association leads to Yng2 deacetylation and degradation, the level of promoter-associated Yng2 is expected to decrease during hyphal induction. Indeed, a time course ChIP of Yng2-Myc showed that Yng2 level decreased after 30 min of hyphal induction (Figures 4F and S4B). The level of promoter-associated Yng2K175R showed a similar decrease, whereas the levels of Yng2-Myc in the hda1 mutant and Yng2K175Q-Myc stayed unchanged (Figures 4F, 5C, and S4C). The level of Esa1, the enzymatic subunit of NuA4, showed a similar decrease at the promoters during hyphal induction (unpublished data).

Bottom Line: Although many regulators have been found involved in hyphal development, the mechanisms of regulating hyphal development and plasticity of dimorphism remain unclear.Maintenance requires promoter recruitment of Hda1 histone deacetylase under reduced Tor1 (target of rapamycin) signaling.Such temporally linked regulation of promoter chromatin by different signaling pathways provides a unique mechanism for integrating multiple signals during development and cell fate specification.

View Article: PubMed Central - PubMed

Affiliation: Department of Biological Chemistry, University of California, Irvine, California, United States of America.

ABSTRACT
Phenotypic plasticity is common in development. For Candida albicans, the most common cause of invasive fungal infections in humans, morphological plasticity is its defining feature and is critical for its pathogenesis. Unlike other fungal pathogens that exist primarily in either yeast or hyphal forms, C. albicans is able to switch reversibly between yeast and hyphal growth forms in response to environmental cues. Although many regulators have been found involved in hyphal development, the mechanisms of regulating hyphal development and plasticity of dimorphism remain unclear. Here we show that hyphal development involves two sequential regulations of the promoter chromatin of hypha-specific genes. Initiation requires a rapid but temporary disappearance of the Nrg1 transcriptional repressor of hyphal morphogenesis via activation of the cAMP-PKA pathway. Maintenance requires promoter recruitment of Hda1 histone deacetylase under reduced Tor1 (target of rapamycin) signaling. Hda1 deacetylates a subunit of the NuA4 histone acetyltransferase module, leading to eviction of the NuA4 acetyltransferase module and blockage of Nrg1 access to promoters of hypha-specific genes. Promoter recruitment of Hda1 for hyphal maintenance happens only during the period when Nrg1 is gone. The sequential regulation of hyphal development by the activation of the cAMP-PKA pathway and reduced Tor1 signaling provides a molecular mechanism for plasticity of dimorphism and how C. albicans adapts to the varied host environments in pathogenesis. Such temporally linked regulation of promoter chromatin by different signaling pathways provides a unique mechanism for integrating multiple signals during development and cell fate specification.

Show MeSH
Related in: MedlinePlus