The Candida albicans biofilm gene circuit modulated at the chromatin level by a recent molecular histone innovation.
Histone H3 and its variants regulate gene expression but the latter are absent in most ascomycetous fungi. Here, we report the identification of a variant histone H3, which we have designated H3VCTG because of its exclusive presence in the CTG clade of ascomycetes, including Candida albicans, a huma...
| Main Authors: | , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Public Library of Science (PLoS)
2019-08-01
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| Series: | PLoS Biology |
| Online Access: | https://doi.org/10.1371/journal.pbio.3000422 |
| _version_ | 1818578246710591488 |
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| author | Laxmi Shanker Rai Rima Singha Hiram Sanchez Tanmoy Chakraborty Bipin Chand Sophie Bachellier-Bassi Shantanu Chowdhury Christophe d'Enfert David R Andes Kaustuv Sanyal |
| author_facet | Laxmi Shanker Rai Rima Singha Hiram Sanchez Tanmoy Chakraborty Bipin Chand Sophie Bachellier-Bassi Shantanu Chowdhury Christophe d'Enfert David R Andes Kaustuv Sanyal |
| author_sort | Laxmi Shanker Rai |
| collection | DOAJ |
| description | Histone H3 and its variants regulate gene expression but the latter are absent in most ascomycetous fungi. Here, we report the identification of a variant histone H3, which we have designated H3VCTG because of its exclusive presence in the CTG clade of ascomycetes, including Candida albicans, a human pathogen. C. albicans grows both as single yeast cells and hyphal filaments in the planktonic mode of growth. It also forms a three-dimensional biofilm structure in the host as well as on human catheter materials under suitable conditions. H3VCTG null (hht1/hht1) cells of C. albicans are viable but produce more robust biofilms than wild-type cells in both in vitro and in vivo conditions. Indeed, a comparative transcriptome analysis of planktonic and biofilm cells reveals that the biofilm circuitry is significantly altered in H3VCTG null cells. H3VCTG binds more efficiently to the promoters of many biofilm-related genes in the planktonic cells than during biofilm growth, whereas the binding of the core canonical histone H3 on the corresponding promoters largely remains unchanged. Furthermore, biofilm defects associated with master regulators, namely, biofilm and cell wall regulator 1 (Bcr1), transposon enhancement control 1 (Tec1), and non-dityrosine 80 (Ndt80), are significantly rescued in cells lacking H3VCTG. The occupancy of the transcription factor Bcr1 at its cognate promoter binding sites was found to be enhanced in the absence of H3VCTG in the planktonic form of growth resulting in enhanced transcription of biofilm-specific genes. Further, we demonstrate that co-occurrence of valine and serine at the 31st and 32nd positions in H3VCTG, respectively, is essential for its function. Taken together, we show that even in a unicellular organism, differential gene expression patterns are modulated by the relative occupancy of the specific histone H3 type at the chromatin level. |
| first_indexed | 2024-12-16T06:42:46Z |
| format | Article |
| id | doaj.art-b094d36a5615467cbb30c39ff1121e87 |
| institution | Directory Open Access Journal |
| issn | 1544-9173 1545-7885 |
| language | English |
| last_indexed | 2024-12-16T06:42:46Z |
| publishDate | 2019-08-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS Biology |
| spelling | doaj.art-b094d36a5615467cbb30c39ff1121e872022-12-21T22:40:39ZengPublic Library of Science (PLoS)PLoS Biology1544-91731545-78852019-08-01178e300042210.1371/journal.pbio.3000422The Candida albicans biofilm gene circuit modulated at the chromatin level by a recent molecular histone innovation.Laxmi Shanker RaiRima SinghaHiram SanchezTanmoy ChakrabortyBipin ChandSophie Bachellier-BassiShantanu ChowdhuryChristophe d'EnfertDavid R AndesKaustuv SanyalHistone H3 and its variants regulate gene expression but the latter are absent in most ascomycetous fungi. Here, we report the identification of a variant histone H3, which we have designated H3VCTG because of its exclusive presence in the CTG clade of ascomycetes, including Candida albicans, a human pathogen. C. albicans grows both as single yeast cells and hyphal filaments in the planktonic mode of growth. It also forms a three-dimensional biofilm structure in the host as well as on human catheter materials under suitable conditions. H3VCTG null (hht1/hht1) cells of C. albicans are viable but produce more robust biofilms than wild-type cells in both in vitro and in vivo conditions. Indeed, a comparative transcriptome analysis of planktonic and biofilm cells reveals that the biofilm circuitry is significantly altered in H3VCTG null cells. H3VCTG binds more efficiently to the promoters of many biofilm-related genes in the planktonic cells than during biofilm growth, whereas the binding of the core canonical histone H3 on the corresponding promoters largely remains unchanged. Furthermore, biofilm defects associated with master regulators, namely, biofilm and cell wall regulator 1 (Bcr1), transposon enhancement control 1 (Tec1), and non-dityrosine 80 (Ndt80), are significantly rescued in cells lacking H3VCTG. The occupancy of the transcription factor Bcr1 at its cognate promoter binding sites was found to be enhanced in the absence of H3VCTG in the planktonic form of growth resulting in enhanced transcription of biofilm-specific genes. Further, we demonstrate that co-occurrence of valine and serine at the 31st and 32nd positions in H3VCTG, respectively, is essential for its function. Taken together, we show that even in a unicellular organism, differential gene expression patterns are modulated by the relative occupancy of the specific histone H3 type at the chromatin level.https://doi.org/10.1371/journal.pbio.3000422 |
| spellingShingle | Laxmi Shanker Rai Rima Singha Hiram Sanchez Tanmoy Chakraborty Bipin Chand Sophie Bachellier-Bassi Shantanu Chowdhury Christophe d'Enfert David R Andes Kaustuv Sanyal The Candida albicans biofilm gene circuit modulated at the chromatin level by a recent molecular histone innovation. PLoS Biology |
| title | The Candida albicans biofilm gene circuit modulated at the chromatin level by a recent molecular histone innovation. |
| title_full | The Candida albicans biofilm gene circuit modulated at the chromatin level by a recent molecular histone innovation. |
| title_fullStr | The Candida albicans biofilm gene circuit modulated at the chromatin level by a recent molecular histone innovation. |
| title_full_unstemmed | The Candida albicans biofilm gene circuit modulated at the chromatin level by a recent molecular histone innovation. |
| title_short | The Candida albicans biofilm gene circuit modulated at the chromatin level by a recent molecular histone innovation. |
| title_sort | candida albicans biofilm gene circuit modulated at the chromatin level by a recent molecular histone innovation |
| url | https://doi.org/10.1371/journal.pbio.3000422 |
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