Filters
Technology
Platform
GSE21571
Saccharomyces cerevisiae
24 Downloadable Samples
Affymetrix Yeast Genome 2.0 Array (yeast2)
Description
The SWR1 complex replaces the canonical histone H2A with the variant H2A.Z (Htz1 in yeast) at specific chromatin regions. This dynamic alteration in nucleosome structure provides a molecular mechanism to regulate transcription. Here we analysed the transcription profiles of single and double mutants and wild-type cells by whole-genome microarray analysis. Our results indicate that genome-wide transcriptional misregulation in htz1 can be partially or totally suppressed if SWR1 is not formed (swr1), if it forms but cannot bind to chromatin (swc2), or if it binds to chromatin but has no histone replacement activity (swc5). These results suggest that in htz1 the nucleosome remodelling activity of SWR1 affects chromatin integrity because of an attempt to replace H2A with Htz1 in the absence of the latter.
Publication Title
The SWR1 histone replacement complex causes genetic instability and genome-wide transcription misregulation in the absence of H2A.Z.
Sample Metadata Fields
No sample metadata fields
View Samples- Saccharomyces cerevisiae
- 6 Downloadable Samples
NextSeq 500
Description
THO/TREX is a conserved complex with a role in messenger ribonucleoprotein biogenesis that links gene expression and genome instability. Here we show that human THO interacts with MFAP1, a spliceosome-associated factor. Interestingly, MFAP1 depletion impairs cell proliferation and genome integrity, increasing ?H2AX foci and DNA breaks. This phenotype is not dependent either on transcription or RNA-DNA hybrids. Mutations in the yeast orthologous gene SPP381, also confer a similar transcription-independent genome instability supporting a conserved role. MFAP1 depletion has a wide effect on splicing and gene expression in human cells, determined by transcriptome analyses, that affects a number of DNA damage response (DDR) genes, which supports an indirect role of MFAP1 on genome integrity. Our work defines a novel functional interaction between THO and RNA processing and argues that splicing factors may contribute to genome integrity indirectly by regulating the expression of DDR genes rather than by a direct role. Overall design: Analysis of gene expression in the Saccharomyces cerevisiae mutant spp381-ts under 1h of restrictive temperature.
Publication Title
Depletion of the MFAP1/SPP381 Splicing Factor Causes R-Loop-Independent Genome Instability.
Sample Metadata Fields
Cell line, Subject
View Samples