GSE173599 deposits menin ChIP at three hours and nowhere else - no 24 h, no 4 d - so the central question this beat raises, whether menin's persistence is fusion-independence or merely a slow off-rate, cannot be answered from the only degron deposit that exists, and the GEO record advertises four-day menin ChIP that was never deposited
also called no menin beyond 3 hours · the missing 24 h menin arm · the overall_design promises what the deposit does not contain
Menin stays on DNA three hours after the cancer protein is destroyed, and the obvious follow-up is to look a day later - but nobody deposited that measurement. The dataset's own description says four-day menin measurements were made, and they are not in the files.
The same thing, for a scientist
**The bounded absence, verified sample by sample against the live GEO supplementary file list on 2026-09-23** [E1]: | channel | timepoints with a deposited peak table | |---|---| | **MEN1 (menin)** | **3 h only** | | DOT1L | 3 h only | | AFF4, CDK9, RNA Pol II, pS2, pS5 | 3 h only | | MLL1 N-term, MLL1c C-term | 3 h only | | HA (the fusion) | 3 h, 24 h, 4 d | | H3K4me3, H3K27ac, H3K79me2, H3K9ac | 3 h, 24 h (H3K27ac also 4 d) | **Every protein channel stops at three hours. Only the fusion's own tag and the histone marks go further.** **Why this is the load-bearing gap for this beat.** Menin retaining 80.0% of its peak calls at 3 h is consistent with two incompatible readings: menin's residence is **genuinely fusion-independent**, or menin simply has a **slow off-rate** and three hours is too early. **A 24 h menin ChIP separates them in one library and it does not exist.** The authors' own language — menin loss is *"more sluggish"*, with *"robust changes only occurring after 3 hours"* [E2] — is explicitly kinetic and makes the slow-off-rate reading the more likely one at the loci they measured. **AND THE DEPOSIT'S OWN DESCRIPTION OVERSTATES ITS CONTENTS.** The GEO `!Series_overall_design` states: *"We also assessed chromatin occupancy changes of MLL-AF9 (HA), DOT1L and Menin in the human MLL-AF9-HA-FKBP12 cells (HCB1) after four days of drug treatment with EPZ-5676, VTP-50469, or DMSO control"* [E1]. **No four-day DOT1L or MEN1 peak table is deposited.** Only HA and H3K27ac have four-day drug arms. Either the processed data was not uploaded or the design statement is inaccurate; the distinction matters because a reader planning a reanalysis from the series description would plan an analysis that cannot be run. **This is why the retention claim in this beat is written as 'at three hours' and not as 'menin is fusion-independent'.**
Scope of the absence, stated so it can be refuted
What was checked: every entry in ftp.ncbi.nlm.nih.gov/geo/series/GSE173nnn/GSE173599/suppl/filelist.txt, 139 lines, parsed for peaks.txt.gz and peaks.xls.gz and grouped by antibody and timepoint. Sample-level GEO records were pulled for the ambiguous ones.
What was NOT checked, and could overturn this: (a) the 23 GB GSE173599_RAW.tar and the per-sample TDF coverage tracks, which were deliberately not downloaded on disk grounds — a TDF is a coverage track and would not contain a peak table, but a 4-day menin TDF would still permit a signal-level analysis; (b) the paper's supplementary tables, which this project has been caught by before when a locus list lived at the publisher rather than in GEO; (c) other deposits entirely — no systematic search for a second MLL-fusion degron with menin ChIP was run.
So the honest scope is: within the deposited peak tables of GSE173599, menin appears at three hours only. The broader claim that no menin ChIP beyond three hours exists under any degron in any deposit is stated but not bounded, and should be treated as a lead rather than a result.
| script | analyses/what-leaves-when-the-fusion-is-degraded/run.py |
|---|---|
| status | run |
| result summary | Menin appears at 3 h only in GSE173599's deposited peak tables. All eight protein channels stop at 3 h; only HA and the four histone marks have later timepoints. The series overall_design describes four-day DOT1L and menin ChIP that is not deposited. |
| preregistration | analyses/what-leaves-when-the-fusion-is-degraded/PREREGISTRATION.md |
| absence class | never-measured |
| absence class basis | Verified sample by sample against the live GEO supplementary file list: every channel stops at 3 h. |
inputs
[ "GSE173599 supplementary file list, 139 entries, parsed by antibody and timepoint" ]
- This project has a documented history of treating a bounded absence as broader than its bound. The narrow claim here - menin appears at 3 h only in this deposit's peak tables - is solid. The broad claim - no menin ChIP beyond 3 h exists under any degron anywhere - is asserted without a search and must not be quoted as though it were the bounded one.
- Do the four-day DOT1L and menin TDF coverage tracks exist in GSE173599_RAW.tar? A targeted download of two files rather than 23 GB would answer it and would turn this absence into an analysable dataset.
- Is there any other MLL-fusion degron deposit with menin ChIP at any timepoint? This has not been searched systematically and is the obvious next literature query.
- If the four-day menin data was collected but not deposited, would the authors share it? This is a tractable request and would resolve the beat's central ambiguity directly.
- E1established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.dataset
Within GSE173599's deposited peak tables, MEN1 ChIP appears at 3 h only, with no 24 h or 4 d arm, and no four-day DOT1L or MEN1 peak table exists despite the series overall_design describing four-day DOT1L and menin ChIP.
GSE173599 supplementary file list and series record (!Series_overall_design), retrieved and parsed 2026-09-23 · Olsen SN, Armstrong SA, et al. · NCBI Gene Expression Omnibus 2022What this evidence cannot show
Bounded to deposited peak tables only. The 23 GB GSE173599_RAW.tar and the per-sample TDF coverage tracks were not downloaded, so a four-day menin coverage track could exist without a peak table. The paper's supplementary tables were not examined for processed occupancy data, and this project has previously found a load-bearing locus list at the publisher rather than in GEO. No systematic search of other deposits for a second MLL-fusion degron with menin ChIP was performed, so the claim is scoped to this deposit.
Evidence that argues against this (1)
- The series overall_design asserts that four-day DOT1L and menin ChIP WAS performed. If so, the measurement exists and could be requested from the authors, which would make this an unavailability rather than an absence - a materially different claim. NCBI Gene Expression Omnibus 2022
- E2strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.paper
The authors describe menin loss after fusion degradation as 'more sluggish' with robust changes only occurring after 3 hours, which is explicitly a kinetic description and makes a later timepoint the decisive missing measurement.
MLL::AF9 degradation induces rapid changes in transcriptional elongation and subsequent loss of an active chromatin landscape. · Olsen SN, Godfrey L, Healy JP, Choi YA, Kai Y, Hatton C, Perner F, Haarer EL, Nabet B, Yuan GC, Armstrong SA · Molecular Cell 2022What this evidence cannot show
The 'sluggish' description refers to their ChIP-qPCR time course at selected loci (15 min, 30 min, 3 h), which does extend the kinetics earlier but not later - their qPCR series also stops at 3 h for menin. So the gap is not merely one of deposition; the experiment appears not to have been run past 3 h for menin by any method.
Evidence that argues against this (1)
- If menin's ChIP-qPCR time course in Figure 4A extends beyond 3 h in the figure itself rather than the text, this absence is weaker than stated. The figure panels were not read at pixel level, only the text describing them. Olsen SN et al. 2022
Each addition in the design closes a named gap in the only relevant deposit, and the later-timepoint arm closes this one: without it, menin's persistence at 3 h cannot be told apart from a slow off-rate.
BOUNDS ITS OWN SIBLING'S CLAIM: because no menin ChIP exists past 3 h, 'menin is fusion-independent' cannot be separated from 'menin has a slow off-rate'. The claim must be read as 'at three hours' and the authors' own word for menin loss is 'sluggish', which is kinetic.
Bounded data-availability statement for menin under a fusion degron: 3 h only in GSE173599's deposited peak tables, despite the series overall_design describing four-day menin ChIP that was never deposited.