Biology subjects

Kubik, S.

Publications and source records attributed to Kubik, S..

3 recordsLinked to original sources

bioRxiv2018

Sfp1 regulates transcriptional networks driving cell growth and division through multiple promoter binding modes

Understanding how transcriptional programs help to coordinate cell growth and division is an important unresolved problem. Here we report that the nutrient- and stress-regulated transcription factor Sfp1 is rate-limiting for expression of several large classes of genes involved in yeast cell growth, including ribosomal protein, ribosome biogenesis, and snoRNA genes. Remarkably, the spectrum of Sfp1 transcription effects is concordant with a combination of chromatin immunoprecipitation and chromatin endogenous cleavage binding analyses, which together provide evidence for two distinct modes of Sfp1 promoter binding, one requiring a co-factor and the other a specific DNA-recognition motif. In addition to growth-related genes, Sfp1 binds to and regulates the promoters of cell cycle \"START\" regulon genes, including the key G1/S cyclins CLN1 and CLN2. Our findings suggest that Sfp1 acts as a master regulator of cell growth and cell size by coordinating the expression of genes implicated in mass accumulation and cell division.

molecular biology↗

bioRxiv2018

General Regulatory Factors control the fidelity of transcription by restricting non-coding and ectopic initiation

The fidelity of transcription initiation is essential for accurate gene expression, but the determinants of start site selection are not fully understood. Rap1 and other General Regulatory Factors (GRFs) control the expression of many genes in yeast. We show that depletion of these factors induces widespread ectopic transcription initiation within promoters. This generates many novel non-coding RNAs and transcript isoforms with diverse stability, profoundly altering the coding potential of the transcriptome. Ectopic transcription initiation strongly correlates with altered nucleosome positioning. We show that Rap1 sterically constrains nucleosomes as its mere binding to the DNA can be sufficient for restoration normal nucleosome positioning, transcription initiation and gene expression. These results demonstrate an essential role for GRFs in the fidelity of transcription initiation and in the suppression of pervasive transcription, redefining current models of their function. They have general implications for the mechanism of transcription initiation and the control of gene expression.\n\nHIGHLIGHTSO_LIRap1, Abf1 and Reb1 control the fidelity of transcription initiation and suppress pervasive transcription\nC_LIO_LIWidespread ectopic transcription initiation in Rap1-deficient cells induces variegated alterations in gene expression\nC_LIO_LIAltered nucleosome positioning in GRFs-defective cells correlate with ectopic transcription initiation.\nC_LIO_LIRap1 controls nucleosomes positioning and transcription initiation at least partially by a steric hindrance mechanism\nC_LI

genomics↗

bioRxiv2018

Sequence-directed action of RSC remodeler and pioneer factors positions +1 nucleosome to facilitate transcription

Accessible chromatin is important for RNA polymerase II recruitment and transcription initiation at eukaryotic promoters. We investigated the mechanistic links between promoter DNA sequence, nucleosome positioning and transcription. Our results indicate that precise positioning of the transcription start site-associated +1 nucleosome in yeast is critical for efficient TBP binding, and is driven by two key factors, the essential chromatin remodeler RSC and a small set of ubiquitous pioneer transcription factors. We find no evidence for recruitment of RSC by pioneer factors, but show instead that the strength and directionality of RSC action on nucleosomes depends upon the arrangement of two specific DNA motifs that promote its binding and nucleosome displacement activity at promoters. Thus, despite their widespread co-localization, RSC and pioneer factors predominantly act independently to generate accessible chromatin. Our results provide insight into how promoter DNA sequence instructs trans-acting factors to control nucleosome architecture and stimulate transcription initiation.

molecular biology↗