Abstract
Centromeres, sites of kinetochore assembly, are important for chromosome stability and integrity. Most eukaryotes have regional centromeres epigenetically specified by the presence of the histone H3 variant CENP-A. CENP-A chromatin is often surrounded by pericentromeric regions packaged into transcriptionally silent heterochromatin. Candida albicans, the most common human fungal pathogen, possesses small regional centromeres assembled into CENP-A chromatin. The chromatin state of C. albicans pericentromeric regions is unknown. Here, for the first time, we address this question. We find that C. albicans pericentromeres are assembled into an intermediate chromatin state bearing features of both euchromatin and heterochromatin. Pericentromeric chromatin is associated with nucleosomes that are highly acetylated, as found in euchromatic regions of the genome; and hypomethylated on H3K4, as found in heterochromatin. This intermediate chromatin state is inhibitory to transcription and partially represses expression of proximal genes and inserted marker genes. Our analysis identifies a new chromatin state associated with pericentromeric regions.
Highlights
The centromere is the cis-acting DNA site of kinetochore assembly and spindle attachment during chromosome segregation in mitosis and meiosis
If the pericentromeric regions of C. albicans were assembled into heterochromatin, genes in proximity to these regions would be poorly expressed
We isolated RNA from wild-type (WT) cells grown at a temperature relevant for growth of C. albicans on the skin (30◦C) and at a temperature mimicking fever in the host (39◦C) and performed RNA-seq analyses
Summary
The centromere is the cis-acting DNA site of kinetochore assembly and spindle attachment during chromosome segregation in mitosis and meiosis. Centromeric regions have a different organization across different species. Some organisms, such as the budding yeast Saccharomyces cerevisiae, have “point” centromeres while other organisms, such as the fission yeast, the fruit fly and human, have “regional” centromeres (Buscaino et al, 2010). Regional centromeres span large DNA domains (∼10 to 10,000 kb) and do not contain a specific DNA sequence but are epigenetically specified by the presence of the histone H3 variant, CENP-A ( termed Cse and CENH3) (Buscaino et al, 2010). Human centromeres are composed of tandem arrays of 171 alpha-satellite repeats and, in Drosophila melanogaster, centromeric DNA contains short repetitive elements interspersed with transposable elements (Buscaino et al, 2010). In the yeast Schizosaccharomyces pombe and the fungal pathogen Candida tropicalis, centromeres are organized in a CENP-A-containing central/mid core domain flanked by inverted repeats
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