Hnf6 (Sp-Hnf6 / SpOnecut; UniProt Q6UAY6) — curation notes

Identity

• UniProt Q6UAY6 (TrEMBL) "One cut domain family member", gene hnf6, EMBL AAQ81630.1, NCBI GeneID 378468.
  The RX line of the UniProt record cites Otim et al. 2004 (PMID:15328009), i.e. the accession is the
  cDNA cloned by the Davidson lab for the GRN work, so there is no identity doubt between the accession
  and the GRN node.
• The same gene was cloned independently as "SpOnecut" by Poustka et al. 2004
  PMID:15230963.
  The UniProt sequence is 483 aa, matching.
• Domain architecture: one CUT domain (residues 272-358) plus a C-terminal homeodomain (387-447),
  the defining ONECUT-class arrangement PMID:15328009.
  PANTHER PTHR14057 (official name "TRANSCRIPTION FACTOR ONECUT"), subfamily SF47 ("HOMEOBOX PROTEIN ONECUT").
• Sea star orthologue AmHNF6 confirms the family placement
  PMID:15661644.

Expression (triphasic)

1. Maternal and global: PMID:15328009
2. Oral ectoderm: after gastrulation the gene is part of the oral ectoderm GRN; it is one of the
   nodal-independent early oral ectoderm genes
   PMID:19268450.
3. Ciliated band: PMID:15328009;
   Poustka et al. independently found PMID:15230963
   and called it PMID:15230963.
   (Poustka did not detect the earlier ubiquitous maternal phase; Otim et al. did by QPCR/WMISH.)
   The ciliary-band phase is conserved in the sea star
   PMID:15661644.

Function in the GRN (loss-of-function, morpholino)

• Skeletogenic (PMC) lineage: Hnf6 is an early, ubiquitously present input into the PMC
  differentiation gene battery, but not into the PMC regulatory genes
  PMID:15328009.
  It is not needed for the micromere signal
  PMID:15328009.
  Oliveri et al. 2008 place it in the skeletogenic GRN as a driver of differentiation genes
  PMID:18413610
  and describe its role as an ancillary booster rather than a lineage-specifying input
  PMID:18413610.
  Summarised by the same group as PMID:15661644.
• Mesoderm: PMID:15328009
  (not annotated: single downstream regulatory gene, direct/indirect unknown).
• Oral ectoderm: PMID:15328009.
  In the Su et al. 2009 oral/aboral ectoderm GRN model, hnf6 is one of four early components of the
  oral regulatory state and is nodal-independent
  PMID:19268450;
  hnf6 knockdown, like dri or gsc knockdown, lets the aboral marker spec1 spread over the whole ectoderm
  PMID:19268450.
• Ciliated band: PMID:15328009

Curation decisions

• GOA has only two IEA rows (DNA binding; nucleus). Both are consistent with a CUT+homeodomain TF.
  DNA binding is modified to the more informative GO:0000981; nucleus accepted (inferred from
  domain content and TF function; no sea urchin immunolocalisation published).
• NEW: GO:0000981 (IMP, Otim 2004), GO:0045944 positive regulation of transcription by RNA polymerase II
  (IMP; knockdown abolishes activation of sm50/pm27/msp130), GO:0070169 positive regulation of biomineral
  tissue development (IMP; the activated genes are the spicule-matrix/biomineralization battery, as for
  the sibling Dri review), GO:0001715 ectodermal cell fate specification (IMP; maintenance of oral
  ectoderm specification, spec1 spreading on knockdown; same term used for Dri).
• Not annotated: ciliated band formation (no GO term exists; proposed as a new term), gatac
  dependence (single downstream regulatory gene), micromere signaling (explicitly negative).
• The proposed GO:0000981 is used rather than the activator child GO:0001228 because no
  cis-regulatory analysis demonstrates direct binding of Hnf6 to a target module; the activator
  inference rests on loss-of-function.
• Only abstracts are cached for Otim 2004, Otim 2005 and Poustka 2004; Oliveri 2008 and Su 2009 are
  full text. A PubMed search (Otim O[Author] AND Davidson EH[Author]) returned no separate Hnf6
  cis-regulatory paper, so none is cited.