MYC notes

This file was created during the ORIGINS_OF_MULTICELLULARITY pass. Automated
deep research was not run for this section; the existing review drew on
MYC-deep-research-falcon.md. Every source below was PubMed-verified, fetched
with just fetch-pmid, and read in its cached full text.

Premetazoan origin (ORIGINS_OF_MULTICELLULARITY, 2026-10-01)

Evidence

Choanoflagellate Myc and Max (Monosiga brevicollis), biochemistry.
Young et al. 2011 (PMID:21571926):
PMID:21571926
PMID:21571926
Their conclusion: PMID:21571926
The partner interface has diverged: PMID:21571926, and PMID:21571926.
N-terminal Myc boxes: PMID:21571926; PMID:21571926. MBI contains the T58/S62 phosphodegron that FBXW7 recognises in human MYC, so this layer of MYC turnover control has no detectable counterpart in the unicellular homologs.
Antagonists: PMID:21571926. The authors speculate that PMID:21571926 (stated as one possibility, not tested).
Ribosome biogenesis regulon (computational). Brown, Cole & Erives 2008 (PMID:18816399):
PMID:18816399;
the regulon PMID:18816399.
Loss tracks Myc loss: PMID:18816399.
Young et al. cite this as a prediction only: PMID:21571926.
Capsaspora repertoire. Sebé-Pedrós et al. 2011 (PMID:21087945):
PMID:21087945;
PMID:21087945.
Capsaspora regulatory genome. Sebé-Pedrós et al. 2016 (PMID:27114036). A Myc-like motif enriched in ATAC-seq sites
PMID:27114036
(the proliferative stage), and PMID:27114036.
Caveat: this is motif inference, not ChIP, and is stated as conditional: PMID:27114036.
Authors' synthesis: PMID:27114036.
Early-branching animal comparator (Hydra). Hartl et al. 2010 (PMID:20142507):
PMID:20142507;
PMID:20142507;
Hydra Myc alone is weak in transformation assays (PMID:20142507),
but PMID:20142507.

Classification of the core functions in the existing review

Core function (review)	Call	Basis
DNA-binding TF activity as a MAX heterodimer (GO:0000981; Myc-Max complex GO:0071943)	Ancestral (at least Choanozoa; Filozoa by gene content)	MbMyc-MbMax heterodimer binds E-boxes and MbMyc is nuclear (PMID:21571926); Capsaspora has Myc, Max, Mnt (PMID:21087945). Transactivation by a unicellular Myc has not been shown directly.
E-box binding (GO:0070888)	Ancestral	CACGTG and non-canonical E-box binding by MbMyc-MbMax (PMID:21571926); Hydra Myc-Max binds CACGTG (PMID:20142507)
Protein dimerization with MAX (GO:0046983)	Ancestral, with a lineage-specific interface	Heterodimerization in M. brevicollis, but no cross-species dimerization with human proteins (PMID:21571926)
Growth control via ribosome biogenesis genes (in description; not a separate core function)	Ancestral (inferred; not directly tested)	E-box RiBi promoter signature in Monosiga (PMID:18816399); Myc-like motif sites at ribosome biogenesis and translation genes in Capsaspora (PMID:27114036)
Positive regulation of cell population proliferation; apoptosis; developmental and tissue-specific roles; oncogenic transformation	Animal-specific as far as documented; unresolved for proliferation	Stem-cell and proliferating-cell expression first documented in Hydra (PMID:20142507). No proliferation, apoptosis or knockout phenotype reported for any unicellular holozoan Myc. Monosiga lacks Mxd/Mnt (PMID:21571926). Hydra Myc1 alone is barely transforming (PMID:20142507).
Repression via MIZ1 (ZBTB17); FBXW7/MBI phosphodegron control	Unresolved / likely animal-specific	MBI (holding the T58/S62 degron) is not detected in MbMyc or Capsaspora Myc (PMID:21571926). No unicellular data on MIZ1-type partners found.

Bottom line: the biochemical core (Max heterodimer, E-box binding, nuclear
transcription factor) is ancestral to choanoflagellates and animals. Regulating
ribosome biogenesis genes is the best-supported candidate for the ancestral
output, but the evidence is computational (promoter motifs, ATAC motif
enrichment). The proliferation, apoptosis, stem-cell and oncogenic roles are
documented only in animals. None of the existing review actions changes.

Track C (IBA nodes and unicellular holozoans), queried 2026-10-01

QuickGO annotation/search?withFrom=PANTHER:<PTN>&taxonId=<T>&taxonUsage=descendants
for T = 28009 (Choanoflagellata), 2687318 (Filasterea), 127916 (Ichthyosporea).

Node	Human IBA terms	Choanoflagellata	Filasterea	Ichthyosporea
PTN001691821	GO:0000978, GO:0000981, GO:0006357	4 rows, all on M. brevicollis MbMyc (A9V5B4): GO:0000978, GO:0000981, GO:0006357, GO:0005634 (is_active_in nucleus)	0	0
PTN002912196	GO:0008284 positive regulation of cell population proliferation	0	0	0

The terms that reach MbMyc are all transcription-factor and nuclear terms,
which match the experimental data on MbMyc (PMID:21571926). No animal
tissue, organ or developmental process term reaches a unicellular organism.
PTN002912196 (proliferation) is placed on a vertebrate-only node. All 58 of
its GOA rows, without a taxon filter, are on vertebrate taxa. That placement
agrees with the absence of evidence for a proliferative role outside animals.
Capsaspora has no Myc rows from either node. Capsaspora is not a PANTHER
reference genome, so it gets no IBA rows; TreeGrafter IEAs were not checked here.