Chromatin mediation of a transcriptional memory effect in yeast.
Previous studies have described a transcriptional "memory effect," whereby transcript levels of many Abf1-regulated genes in the budding yeast Saccharomyces cerevisiae are undiminished even after Abf1 has dissociated from its regulatory sites. Here we provide additional support for this effect and investigate its molecular basis. We show that the effect is observed in a distinct abf1 ts mutant from that used in earlier studies, demonstrating that it is robust, and use chromatin immunoprecipitation to show that Abf1 association is decreased similarly from memory effect and transcriptionally responsive genes at the restrictive temperature. We also demonstrate that the association of TATA-binding protein and Pol II decreases after the loss of Abf1 binding for transcriptionally responsive genes but not for memory effect genes. Examination of genome-wide nucleosome occupancy data reveals that although transcriptionally responsive genes exhibit increased nucleosome occupancy in abf1 ts yeast, the promoter regions of memory effect targets show no change in abf1 ts mutants, maintaining an open chromatin conformation even after Abf1 eviction. This contrasting behavior reflects different inherent propensity for nucleosome formation between the two classes, driven by the presence of A/T-rich sequences upstream of the Abf1 site in memory effect gene promoters. These sequence-based differences show conservation in closely related fungi and also correlate with different gene expression noise, suggesting a physiological basis for greater access to "memory effect" promoter regions. Thus, our results establish a conserved mechanism underlying a transcriptional memory effect whereby sequences surrounding Abf1 binding sequences affect local nucleosome occupancy following loss of Abf1 binding. Furthermore, these findings demonstrate that sequence-based differences in the propensity for nucleosome occupancy can influence the transcriptional response of genes to an altered regulatory signal.
Laboratory of Molecular Genetics, Wadsworth Center, New York State Department of Health, Albany, New York Department of Biomedical Science, University at Albany School of Public Health, Albany, New York.
Emily
E
Paul
Department of Molecular Genetics, Weizmann Institute of Science, Rehovot, Israel.
Itay
I
Tirosh
Department of Biochemistry and the Center of Excellence in Bioinformatics and Life Sciences, State University of New York at Buffalo, Buffalo, New York.
William
W
Lai
Department of Biochemistry and the Center of Excellence in Bioinformatics and Life Sciences, State University of New York at Buffalo, Buffalo, New York.
Michael J
MJ
Buck
Laboratory of Molecular Genetics, Wadsworth Center, New York State Department of Health, Albany, New York.
Michael J
MJ
Palumbo
Laboratory of Molecular Genetics, Wadsworth Center, New York State Department of Health, Albany, New York Department of Biomedical Science, University at Albany School of Public Health, Albany, New York randall.morse@health.ny.gov.
Randall H
RH
Morse
D001665:Binding Sites; D002843:Chromatin / Q000235:genetics* / Q000378:metabolism; D005656:Fungal Proteins / Q000235:genetics / Q000378:metabolism; D015966:Gene Expression Regulation, Fungal; D009154:Mutation; D009707:Nucleosomes / Q000378:metabolism; D011401:Promoter Regions, Genetic; D011485:Protein Binding; D014157:Transcription Factors / Q000378:metabolism; D014158:Transcription, Genetic; D015003:Yeasts / Q000235:genetics* / Q000378:metabolism
D002843:Chromatin; D005656:Fungal Proteins; D009707:Nucleosomes; D014157:Transcription Factors
Abf1; ChIP-seq; chromatin; nucleosome; transcription; yeast