SWI4 (P25302, YER111C) — working notes

Saccharomyces cerevisiae S288c. 1093 aa. Alternative name ART1. SGD:S000000913.
UniProt domain map: APSES/KilA-N HTH DNA-binding domain (37-147, HTH 71-92), four
central ankyrin repeats, conserved C-terminal Swi6-binding region; Cdk1 phosphosites at
Ser255 and Ser806 recorded from the Holt et al. 2009 phosphoproteome.

1. Biology in brief

SBF DNA-binding subunit. Swi4 is the sequence-specific DNA-binding subunit of SBF
(SCB-binding factor), the Swi4-Swi6 heterodimer that drives the Start (G1/S)
transcriptional program. The discovery papers identified the "cell-cycle box" of the HO
promoter and the two SWI genes that act through it
PMID:3542227
PMID:2649246,
and cloning of SWI4 placed the protein physically in that complex
PMID:2689885.

SCB elements and the division of labour with Swi6. The DNA-recognition function sits
in Swi4, the regulatory function in Swi6
PMID:1465410
PMID:8423776.
The N-terminal domain suffices for SCB recognition in vitro
PMID:10490612,
the SCB consensus is CA/GCGAAA
PMID:20641022,
and protein-binding microarrays recover the same motif class
PMID:19111667.
Swi4 and Mbp1 are the alternative DNA-binding subunits of the sister complexes SBF and MBF
PMID:10490612.

C-terminal auto-inhibition relieved by Swi6. Full-length Swi4 does not bind SCBs alone
because its C terminus folds back onto the DNA-binding domain; Swi6 binding to that C
terminus releases it
PMID:10490612.
The inhibitory contact is intramolecular: Swi4 is monomeric and SBF is a 1:1 heterodimer
PMID:10490612
PMID:10490612.
The C terminus is necessary and sufficient for Swi6 association and dispensable for DNA binding
PMID:8423776,
and overproduced Swi4 can bypass Swi6 for HO transcription
PMID:8423776.

Localization. Swi4 is nuclear at every cell-cycle stage, in contrast to Swi6
PMID:10490612
PMID:10490612.
ChIP-chip and ChIP-PCR place it on promoter chromatin
PMID:12464632
PMID:12464632.

Whi5 repression and Start. SBF sits on G1/S promoters in early G1 bound by the
corepressor Whi5, which is removed by Cln3-Cdc28 phosphorylation (the Rb/E2F analogy)
PMID:15210110
PMID:15210110
PMID:15210111.
The essential output of SBF (with MBF) is G1 cyclin transcription
PMID:1832338
PMID:1832338
PMID:10490612.
Shut-off after G1 involves mitotic Clb2-Cdc28 binding the Swi4 ankyrin repeats
(Siegmund and Nasmyth 1996, not in the publication cache; taken from the deep-research
synthesis)
[file:yeast/SWI4/SWI4-deep-research-falcon.md "Four ankyrin repeats mediate protein interactions, including association with mitotic Clb2–Cdc28/Cdk1."].

Slt2/Mpk1 cell-wall-integrity pathway. Independently of Start, Swi4 is the
transcription factor engaged non-catalytically by the CWI MAP kinase Mpk1 (Slt2) and its
pseudokinase paralog Mlp1: activated Mpk1 docks on Swi4, confers DNA binding without
Swi6, and Swi6 is recruited afterwards
PMID:18268013
PMID:18268013
PMID:20641022.
Reporter genes for this branch (FKS2, CHA1, YKR013w, YLR042c) are induced by several
cell-wall stresses, heat being the strongest
PMID:20641022
PMID:20641022
PMID:20641022.

Other regulation (orientation only, from the deep-research file). Whi5 and Swi6
phosphorylation are partly redundant routes to SBF activation, Bck2 gives a
Cln3-independent input, and during meiotic entry SBF is silenced jointly by Whi5 and a
long undecoded SWI4 transcript isoform (LUTI) that represses the canonical promoter
(Su et al. 2024). None of this is used to grade an annotation.

2. Publication cache status

Full text cached: PMID:10490612 (Baetz and Andrews 1999), PMID:12464632 (Horak 2002),
PMID:20641022 (Kim and Levin 2010), PMID:21179020 (Lambert 2010), PMID:37968396
(Michaelis 2023). Abstract only: PMID:3542227, PMID:2649246, PMID:2689885, PMID:1832338,
PMID:1465410, PMID:8423776, PMID:18268013, PMID:16429126, PMID:19111667, PMID:25112483.
Every quote in the review YAML is from the cached text; for abstract-only papers the
claims used are all in the abstract. The SBF-complex IDA from PMID:1832338 rests on
full-text gel-shift data that is not cached and is deferred to the SGD curator.

3. Key curation decisions

35 GOA rows, 35 rows in existing_annotations. Tally: ACCEPT 24, MODIFY 4, REMOVE 6,
KEEP_AS_NON_CORE 1.

4. Core functions

  1. SCB-binding, Pol II-activating subunit of SBF driving the G1/S regulon (CLN1, CLN2,
    PCL1, PCL2, HO, cell-wall and bud-emergence genes); nucleus, chromatin; in SBF.
  2. Transcription factor engaged non-catalytically by Mpk1/Mlp1 under cell-wall stress,
    binding FKS2/CHA1/YKR013w/YLR042c promoters independently of Swi6 before Swi6 is
    recruited; nucleus, chromatin. Process: GO:0045944 (the heat term is graded non-core).

5. Session log