Hes7 (mouse) review notes

UniProt Q8BKT2 (HES7_MOUSE), transcription factor HES-7, 225 aa. PANTHER PTHR10985
(BASIC HELIX-LOOP-HELIX TRANSCRIPTION FACTOR, HES-RELATED). Notch-module role: Notch
target gene / segmentation-clock transcriptional repressor (Hairy/E(spl) class).

Structure / molecular function

• bHLH-Orange repressor with C-terminal WRPW Groucho/TLE-recruitment motif
  PMID:11260262
• Represses N-box and E-box promoters in transfection
  PMID:11260262
• Binds N-boxes of the Lfng promoter and of its own promoter and represses them
  PMID:16342160
• UniProt: "Transcriptional repressor. Represses transcription from both N box- and E box-containing promoters."
  Groucho/TLE interaction by similarity only (ECO:0000250).

Notch pathway position

• Expression is Notch-dependent (direct Notch target)
  PMID:11260262
• Human HES7 is described as a direct Notch target and part of a negative feedback that attenuates Notch
  signalling PMID:18775957
• Msgn1 + Notch activate Hes7/Lfng; Hes7 is the short-lived periodic repressor
  PMID:21750544

Segmentation clock / somitogenesis

• mRNA oscillates with 2-h period in PSM; null mice have unsegmented somites, lost A-P
  polarity; vertebrae/ribs disorganized; Lfng expressed continuously
  PMID:11641270
• Protein oscillation depends on proteasomal degradation; negative autoregulatory feedback
  PMID:12783854
• Protein instability (half-life ~22 min) is required for sustained oscillation
  PMID:15170214
• In Hes7-/- mice somites still form but irregularly PMID:19779553
• Heterozygotes show kinked tails (dose sensitivity) PMID:11641270
• Human HES7 missense in DNA-binding domain causes autosomal recessive spondylocostal dysostosis (SCDO4)
  PMID:18775957.

Expression

• PSM-restricted in mouse embryo PMID:11260262.
  This argues that IBA "regulation of neurogenesis" (from deep HES family node PTN000105428) is not
  applicable to Hes7, which is not a neural Hes.

Pathway-variant relevance

• Hes7 is a vertebrate (mammalian) PSM-specific Hes paralog; functional analogs are zebrafish her1/her7
  and chick hairy1/2; Drosophila has E(spl)/hairy. Clock uses negative autoregulation, not Notch-receptor
  activity per se.

Deep research

Falcon deep research completed (Hes7-deep-research-falcon.md; wrapper reported a 600 s timeout but the
falcon client finished and wrote the file). It additionally reports Hes7-dependent oscillation of Dll1 and
Dusp4 (citing 2024-2025 reviews; not independently verified here)
[file:mouse/Hes7/Hes7-deep-research-falcon.md "Hes7 functions as a sequence-specific DNA-binding transcriptional repressor that recognizes and binds N-box regulatory sequences in target gene promoters"].

2026-10-12 Ortholog/family audit (Dll1, Dll3, Hes7, Rbpj)

• GOA refreshed: no new rows, coverage complete. There is no human HES7 review in the repo; compared with zebrafish her1 (a segmentation-clock Hes paralog).
• Agreement: both have core MF GO:0001227 (Pol II-specific repressor) with negative regulation of Pol II transcription and somitogenesis. IBAs for GO:0000981, GO:0000978, GO:0000122 and nucleus (PTN004213585) are accepted in both, and A/P pattern specification (PTN000105428) is non-core in both.
• Difference kept: IBA GO:0050767 regulation of neurogenesis (PTN000105428) is MARK_AS_OVER_ANNOTATED for Hes7 but KEEP_AS_NON_CORE for her1. Hes7 has explicit target-specific evidence of divergence PMID:11260262; the her1 review found no such evidence. The Hes7 reason now records this.
• Status set to COMPLETE.