Search bioRxivSearch

Biology subjects

Descrimes, M.

Publications and source records attributed to Descrimes, M..

2 recordsLinked to original sources

Transcription-dependent spreading of canonical yeast GATA factor across the body of highly expressed genes

GATA transcription factors are highly conserved among eukaryotes and play roles in transcription of genes implicated in cancer progression and hematopoiesis. However, although their consensus binding sites have been well defined in vitro, the in vivo selectivity for recognition by GATA factors remains poorly characterized. Using ChIP-Seq, we identified the Dal80 GATA factor targets in yeast. Our data reveal Dal80 binding to a large set of promoters, sometimes independently of GATA sites. Strikingly, Dal80 was also detected across the body of promoter-bound genes, correlating with high, Dal80-sensitive expression. Mechanistic single-gene experiments showed that Dal80 spreading across gene bodies is independent of intragenic GATA sites but requires transcription elongation. Consistently, Dal80 co-purified with the post-initiation form of RNA Polymerase II. Our work suggests that GATA factors could play dual, synergistic roles during transcription initiation and post-initiation steps, promoting efficient remodeling of the gene expression program in response to environmental changes.\n\nAuthor SummaryGATA transcription factors are highly conserved among eukaryotes and play key roles in cancer progression and hematopoiesis. In budding yeast, four GATA transcription factors are involved in the response to the quality of nitrogen supply. We have determined the whole genome binding profile of one of them, Dal80, and revealed that it also binds across the body or promoter-bound genes. Our observation that ORF binding correlated with elevated transcription levels and exquisite Dal80 sensitivity suggests that GATA factors could play other, unexpected roles at post-initiation stages in eukaryotes.

genomics

Dose-dependency of heterochromatin domains reveals subtelomeric structuration in budding yeast

The eukaryotic genome is divided into chromosomal domains of heterochromatin and euchromatin. Transcriptionally silent heterochromatin is found at subtelomeric regions, leading to the telomeric position effect (TPE) in yeast, fly and man. Heterochromatin generally initiates and spreads from defined loci, and diverse mechanisms prevent the ectopic spread of heterochromatin into euchromatin. Here, we overexpressed the silencing factor Sir3 at various levels in yeast, and found that Sir3 spreading into Extended Silent Domains (ESD) eventually reached saturation at subtelomeres. We observed that Sir3 spreading into ESDs covered zone associated with specific histone marks in wild-type cells and stopped at zones of histone mark transitions including H3K79 tri-methylation levels. The conserved enzyme Dot1 deposits H3K79 methylation, and we found that it is essential for viability upon overexpression of Sir3, but not of a spreading-defective mutant Sir3A2Q. These data suggest that H3K79 methylation actively blocks Sir3 spreading. Lastly, our meta-analysis uncovers previously uncharacterized discrete subtelomeric domains associated with specific chromatin features offering a new viewpoint on how to separate subtelomeres from the core chromosome.

genomics