SoxB1 (Q9Y0D7, Strongylocentrotus purpuratus) — curation notes

Identity

UniProt Q9Y0D7 (TrEMBL, Q9Y0D7_STRPU, "Transcription factor SoxB1", EMBL AAD40688.3)
is the SpSoxB1 cDNA reported by Kenny et al. 1999 (Development 126:5473; the RX
reference on the record) PMID:10556071. 344 aa; HMG box (DNA_BIND) at
residues 61-129; Pfam HMG_box (PF00505) + SOXp (PF12336); InterPro IPR022097 SOX family.
PANTHER PTHR10270:SF324 on the record (label not asserted here; see CLAUDE.md).
Community names: SpSoxB1, SoxB1, soxb1. SoxB-group (Sox1/2/3-like) HMG-box factor; Wei
et al. 2011 note that "SoxB1 is most closely related to Sox1, Sox2, and Sox3, which have
been shown to maintain a neural precursor state in mouse embryos" PMID:21576476. The
paralog SpSoxB2 is a distinct gene with partly distinct functions PMID:14499650.
No identity doubt: the accession, the RX paper, the EMBL entry and the GRN literature
all refer to the same maternal SoxB1 gene product.

Maternal mRNA is uniform in the egg; protein is nuclear in all cells of 4- and 8-cell
embryos, then lost from micromere nuclei at 4th cleavage PMID:10556071.
Zygotic transcription is nonvegetal, and the nuclear-SoxB1-free vegetal domain expands
until only ectoderm retains nuclear protein PMID:10556071. It is "the earliest
known spatially restricted regulator of transcription along the animal-vegetal axis of
the sea urchin embryo" PMID:10556071.
Clearance from vegetal lineages is post-translational and beta-catenin dependent
PMID:15689377. Macromere turnover requires nuclear entry; mesomeres (ectoderm)
do not turn it over but show negative autoregulation PMID:15689377. SpKrl (Blimp1/Krox),
a direct beta-catenin/TCF target, represses soxb1 transcription PMID:11152635.
In the Davidson micromere GRN, absence of nuclear SoxB1 is one of the three initial
micromere-specific character states [PMID:18413610 "Concomitantly, the maternal
transcription factor SoxB1 enters the nuclei of all early cleavage blastomeres except the
micromeres (ref. 28 and Fig. S4 )." ... "SoxB1 is believed to act as an antagonist of the
transcriptional cofactor function of β-catenin."].

SpSoxB1 binds the Sox cis element of the SpAN (tolloid/BMP1-related) promoter in EMSA;
the antiserum supershifts the nuclear-extract complex PMID:10556071.
The Sox site is essential in vivo (20-fold) but SoxB1 does not act as a classical
activator; it bends DNA and works architecturally [PMID:11763999 "Regulatory sites that
bind SpSoxB1 and CBF (CCAAT binding factor) are essential for strong transcriptional
activity because mutations of these elements reduce promoter activity in vivo 20- and
10-fold, respectively." ; "Here we show that multimerized SpSoxB1 elements cannot
activate transcription from the SpAN basal promoter in vivo." ; "However, like other
factors containing HMG-class DNA binding domains, SpSoxB1 does induce strong bending of
DNA." ; "The results described above suggest a model in which SpSoxB1 promotes
transcription of the SpAN gene primarily through DNA bending, rather than through
transcriptional activation."]. Circular-permutation EMSAs with in vitro translated
protein were used to show the bending (full text cached).

Overexpression animalizes: PMID:14499650. The effect is at the protein-protein level, not
via DNA binding PMID:14499650.
Loss of function raises TCF/beta-catenin reporter output in vivo, i.e. SoxB1 normally
dampens canonical Wnt/beta-catenin transcriptional output PMID:14499650. Summarised in Angerer 2005 PMID:15689377.
Paradoxically, normal SoxB1 is also required for gastrulation and endoderm
differentiation PMID:14499650. The authors
attribute this to SoxB target genes required for gastrulation, not to SoxB1 being an
endoderm specifier; this is treated as an indirect/pleiotropic requirement here.

nodal cis-regulation: the 5' module of nodal has essential Sox sites, and zygotic nodal
and univin expression depend on SoxB1 PMID:17855430.
Ciliated-band and ectoderm regulatory states: soxb1 MASO downregulates nearly all CB
regulatory genes [PMID:25655703 "Remarkably, almost all of the regulatory genes
specifically expressed within these domains are downregulated by interference with
SoxB1 expression, implying their common activation by this factor." ; "However, most of
its target genes utilize SoxB1 as a transcriptional activator."]. It is described as
"a pan-ectodermal transcription factor that is known to affect many other regulatory
genes of the oral and aboral ectoderm GRNs" PMID:25655703. Negative autoregulation and
repression of otx beta1/2 are also seen [PMID:25655703 "As these analyses show, SoxB1
controls its own level of expression through negative feedback on the soxb1 gene, so that
soxb1 MASO produces a large increase in the prevalence of its own mRNA." ; "Furthermore,
SoxB1 evidently represses otxβ1/2 transcription."].
Slota et al. 2018 count soxb1 among the proneural TFs expressed in all three neural
territories and note its earlier ectoderm role PMID:30413529.

SoxB1 marks uncommitted neural precursors and is lost from differentiating neurons in
ectoderm and foregut PMID:21576476. Persistent foregut SoxB1 is
proposed to preserve neural potential there by antagonising Wnt/beta-catenin PMID:21576476. Because soxb1 knockdown blocks gastrulation, its requirement for foregut
neurons could not be tested PMID:21576476.
Slota 2018 used a soxb1 MO and found domain-specific effects on other proneural genes
PMID:30413529. Neural involvement is real but pleiotropic and mostly expression-based, so
the IBA neuron differentiation row is kept as non-core rather than promoted.

IBA MF rows (GO:0000978 cis-regulatory DNA binding, GO:0001228 activator) ACCEPT: EMSA
binding to the SpAN Sox element; the site is essential in vivo; most ectoderm targets use
SoxB1 as an activator. Caveat recorded that SpAN activation is architectural (DNA
bending) rather than classical transactivation.
IBA BP GO:0045944 ACCEPT (core); GO:0000122 KEEP_AS_NON_CORE (negative autoregulation,
otx beta1/2 repression); GO:0030182 neuron differentiation KEEP_AS_NON_CORE; GO:0007420
brain development MARK_AS_OVER_ANNOTATED (echinoderm embryos have an apical organ, not a
brain; vertebrate/fly-seeded node).
IEA rows (DNA binding, nucleus, regulation of transcription) ACCEPT as generic parents.
NEW: GO:0090090 negative regulation of canonical Wnt signaling pathway (IMP, Kenny 2003);
GO:0008301 DNA binding, bending (IDA, Kenny 2001); GO:0001715 ectodermal cell fate
specification (IMP, Barsi 2015 + Kenny 2003 animalisation).
Not proposed: endoderm/gastrulation terms (requirement is indirect); GO:0000981 (ancestor
of the accepted GO:0001228 row); neurogenesis-specific terms (expression-based).
gocams/index.tsv has no entry for Q9Y0D7/SoxB1.
PMID:26511925 (Garner et al. 2016) was fetched while screening neurogenesis literature but
concerns SoxB2/SoxC and is not cited.