Kar4 acts as a Ste12 regulator in Saccharomyces cerevisiae , promoting Ste12 binding to a specific DNA motif genome-wide

2025 · doi:10.64898/2025.12.09.693310
preprint OA: closed
Full text JSON View at publisher
⚙ AI-generated summary by claude@2026-07, 2026-07-14 ⓘ

Kar4 enhances Ste12 binding specificity genome-wide to head-to-tail arranged pheromone response elements, preventing aberrant gene activation during yeast mating pheromone response.

One-sentence paraphrase of the abstract; not a substitute for reading it. No clinical advice. How this works

⚙ AI-generated deep summary by claude@2026-07, 2026-07-14 · read from full text ⓘ

This paper investigates how the yeast protein Kar4 regulates Ste12, the master transcription factor of the mating pheromone response in Saccharomyces cerevisiae, by combining RNA-seq to measure transcriptional changes with ChIP-exo to map Ste12 DNA binding. The authors find that Kar4 promotes Ste12 occupancy at nearly all Ste12 sites linked to transcriptionally upregulated genes, even when upregulation is not Kar4-dependent, and that most Ste12 sites contain a specific two-PRE head-to-tail motif separated by four nucleotides (H-T 4). They report that Kar4-dependent genes have PREs with more mismatches and lower Ste12 binding in kar4Δ cells, while in kar4Δ cells Ste12 binds increasingly to non–H-T 4 motifs (especially T-T 3), leading to abnormal upregulation of genes normally not transcribed during the wild-type response. The paper’s caveat is its focus on the yeast mating pheromone system, so its mechanistic conclusions are constrained to that biological context. The paper does not explicitly discuss endometriosis or adenomyosis; it was included in the corpus via a keyword match in the upstream search index.

Read from the paper's body, not the abstract. Not a substitute for reading the paper. No clinical advice. How this works

Abstract

Kar4 is a putative transcription factor required for efficient mating in the budding yeast Saccharomyces cerevisiae . Kar4 functions with Ste12, the master transcriptional regulator of the yeast mating pheromone response, to promote the transcription of a subset of Ste12 targets required for mating. However, the mechanism by which Kar4 modulates Ste12 activity has remained uncertain. Here, we examined Kar4’s function at the levels of transcription (RNA-seq) and Ste12 DNA binding (ChIP-exo). We show that Kar4 promotes Ste12 binding to nearly all Ste12 DNA-binding sites associated with transcriptionally-upregulated genes, even if their upregulation is not dependent on Kar4. We further found that the majority of Ste12-binding sites have two pheromone response elements (PREs) separated by four nucleotides in a head-to-tail orientation (H-T 4 motif). Sites associated with Kar4-dependent transcription have PREs with more mismatches and substantially lower Ste12 occupancy in kar4 Δ cells than sites linked to Kar4-independent transcription. During the pheromone response in kar4 Δ cells, Ste12 exhibits increased binding to non-H-T 4 motifs, particularly T-T 3 motifs, resulting in the abnormal upregulation of many genes not transcribed during the wild-type pheromone response. Therefore, we propose that Kar4 functions by increasing the DNA-binding specificity of Ste12 globally, promoting its binding primarily to H-T 4 motifs. Our model is consistent with previously-observed slower induction kinetics of Kar4-dependent genes via a feed-forward mechanism. Lastly, we uncovered several novel aspects of the pheromone response, including a broad role for the Crz1 transcription factor, induction of stress responses, and the identification of pheromone-responsive intergenic transcripts.
Full text 2,035 characters · extracted from oa-doi-fallback · click to expand
Abstract Kar4 is a putative transcription factor required for efficient mating in the budding yeast Saccharomyces cerevisiae. Kar4 functions with Ste12, the master transcriptional regulator of the yeast mating pheromone response, to promote the transcription of a subset of Ste12 targets required for mating. However, the mechanism by which Kar4 modulates Ste12 activity has remained uncertain. Here, we examined Kar4’s function at the levels of transcription (RNA-seq) and Ste12 DNA binding (ChIP-exo). We show that Kar4 promotes Ste12 binding to nearly all Ste12 DNA-binding sites associated with transcriptionally-upregulated genes, even if their upregulation is not dependent on Kar4. We further found that the majority of Ste12-binding sites have two pheromone response elements (PREs) separated by four nucleotides in a head-to-tail orientation (H-T 4 motif). Sites associated with Kar4-dependent transcription have PREs with more mismatches and substantially lower Ste12 occupancy in kar4Δ cells than sites linked to Kar4-independent transcription. During the pheromone response in kar4Δ cells, Ste12 exhibits increased binding to non-H-T 4 motifs, particularly T-T 3 motifs, resulting in the abnormal upregulation of many genes not transcribed during the wild-type pheromone response. Therefore, we propose that Kar4 functions by increasing the DNA-binding specificity of Ste12 globally, promoting its binding primarily to H-T 4 motifs. Our model is consistent with previously-observed slower induction kinetics of Kar4-dependent genes via a feed-forward mechanism. Lastly, we uncovered several novel aspects of the pheromone response, including a broad role for the Crz1 transcription factor, induction of stress responses, and the identification of pheromone-responsive intergenic transcripts. Competing Interest Statement The authors have declared no competing interest. Footnotes ↵* Co-first author Supplemental Figures and Appendix added. For Supplemental Files containing quantification of raw data, please contact O.C-F.

Text is read by the "Ask this paper" AI Q&A widget below. Extraction quality varies by source — PMC NXML preserves structure cleanly, OA-HTML may include some navigation residue, and OA-PDF can have broken hyphenation. The publisher copy (via DOI) is the canonical version.

My notes (saved in your browser only)

⚙ Ask this paper AI returns verbatim quotes from the full text · source: oa-doi-fallback ⓘ

Answers must be backed by verbatim quotes from this paper's full text. Hallucinated quotes are dropped automatically; if no verbatim passage answers the question, we say so. How this works

Citation neighborhood (no data yet)

We don't have any in-corpus citations linked to this paper yet. This is a recent paper (2025) — citers typically take a year or two to land, and the OpenAlex reference graph may still be filling in.

Source provenance

europepmc
last seen: 2026-05-20T01:45:00.602351+00:00