Dri (Strongylocentrotus purpuratus, UniProt Q8MQH7) - curation notes

Identity

• UniProt Q8MQH7 (DRI_STRPU, Swiss-Prot reviewed, 490 aa, EMBL AY130972 /
  AAM81746) is Spdeadringer (Spdri), deposited by the Davidson lab; its single RX
  line is PMID:12941621 (Amore et al. 2003), the paper that cloned and named the
  gene. The community symbol in the GRN literature is dri / Spdri; here the
  folder alias is Dri.
• Domain architecture (UniProt FT): ARID DNA-binding domain at 202-294 (PROSITE
  PS51011) and a C-terminal REKLES domain at 389-479 (PS51486), the two-domain
  architecture diagnostic of the ARID3 / Dead ringer / Bright subfamily (InterPro
  IPR045147 "ARI3A/B/C"). PANTHER PTHR15348:SF0 (label not written from memory).
  No identity doubt: the accession, the RX paper and the GRN gene are the same
  entity.

What the gene is

• PMID:12941621
• PMID:12941621

Expression (biphasic)

• PMID:12941621
• Timing matters for the choice of GO terms: PMID:12941621 Dri is therefore not a specification gene in either
  territory; it is deployed after the skeletogenic and oral-ectoderm regulatory
  states are already installed, and acts to drive differentiation-gene
  batteries (PMCs) or to maintain/elaborate the oral regulatory state.
• UniProt DEVELOPMENTAL STAGE (from the same paper): later expression in apical
  plate and ciliary band of the post-gastrular embryo.

Place in the skeletogenic (PMC) GRN

• Inputs: dri is downstream of the double-negative-gate regulators. In the
  Oliveri/Tu/Davidson 2008 synthesis: PMID:18413610 Cis-regulatory dissection of the spdri locus confirms the
  inputs: PMID:18718463
• Outputs: Dri, with Ets1, is a driver of the terminal skeletogenic
  differentiation gene battery. PMID:12941621 PMID:18413610
• Direct, positive cis-regulatory input (the key MF evidence): on the Sp-cyp1
  (cyclophilin) 218-bp module, PMID:16574094 The authors generalise: PMID:16574094
• Loss of function: PMID:12941621 Micromere-transplant chimeras separate the
  autonomous from the non-autonomous requirement: PMID:12941621

Place in the oral ectoderm GRN

• PMID:12941621
• Knockdown converts the whole ectoderm to aboral character: PMID:12941621 Su et al. 2009 cite this as one
  of the perturbations showing the oral GRN controls the aboral repressor:
  PMID:19268450
• Position in the Su 2009 oral ectoderm GRN: dri belongs to the set released by
  the Gsc "repressor A" gate (the oral-ectoderm analogue of the HesC gate):
  PMID:19268450 Its later domain is the oral "face":
  PMID:19268450
• Cis-regulation (Mahmud & Amore 2008): a 4.7 kb fragment (-3456;+389) with a
  GFP reporter reproduces both expression phases, and PMID:18718463 The reporter responds to Dri itself,
  implying autoregulation.

Pleiotropic / indirect effects (not annotated)

• Gastrulation failure after dri MASO is indirect: PMID:12941621 It is attributed partly to a late micromere
  signalling function needed to clear SoxB1 from the prospective endoderm and
  partly to a non-autonomous oral ectoderm effect. Not a Dri participation in
  gastrulation; no BP term proposed.

GOA audit (all electronic)

• Six rows, three IBA (PAINT, PTN000394188) and three IEA (InterPro ARID
  domain; ARBA/UniProt subcellular). DNA binding, nucleus and regulation of
  transcription by RNA polymerase II are all correct for an ARID-class TF; DNA
  binding is under-specific and the literature supports the RNA polymerase II
  cis-regulatory-region sequence-specific child. No GO-CAM contains Q8MQH7
  (gocams/index.tsv).

Decisions

• NEW GO:0001228 (IDA, PMID:16574094): direct positive cis-regulatory input on
  Sp-cyp1 is shown by site mutation and reporter loss.
• NEW GO:0045944 (IMP, PMID:12941621; IDA, PMID:16574094).
• NEW GO:0070169 positive regulation of biomineral tissue development (IMP,
  PMID:12941621): autonomous requirement for skeletogenic gene expression and
  failure of spiculogenesis; matches the convention used for Alx1 and Ets1.
• NEW GO:0001715 ectodermal cell fate specification (IMP, PMID:12941621) for
  the oral-ectoderm role: Dri is part of the GRN that establishes/maintains
  oral (vs aboral) ectodermal identity; the project convention (Otx, Eve,
  SoxB1) uses this term for sub-ectodermal regional fates. GO:0060834
  oral/aboral axis specification exists but carries no annotations in QuickGO,
  so it is raised as a question rather than asserted.
• Not proposed: mesodermal cell fate specification (Dri follows specification),
  gastrulation (indirect), EMT (dri is needed until ingression but no ingression
  defect is described as Dri-autonomous).