Biochemistry, Genetics and Molecular Biology› Molecular Biology› Epigenetics and DNA Methylation

Innate immune memory — Polycomb group proteins as carriers of LPS memory

Submitted 2026-10-23

Field: Biochemistry, Genetics and Molecular Biology › Molecular BiologyType: No effect foundArea: innate immune memoryTarget: Polycomb group proteins as carriers of LPS memoryStage: preclinical

Hypothesis

Polycomb group proteins, which keep a memory of developmental signals in chromatin, would also keep a memory of earlier exposure to bacterial lipopolysaccharide (LPS) and change the response to a second exposure.

What failed

In reporter cells, neither a single nor repeated LPS pre-treatment changed how strongly LPS-responsive genes switched on after a second exposure.

Broken assumption

Polycomb-based chromatin memory also stores the memory of earlier immune stimulation.

Why

The abstract does not give a cause. Under these conditions the Polycomb system did not record LPS exposure.

From the published paper: Geigges et al. PLoS ONE, 2020. ↗CC BY

Research ideas from this failure

Unvetted lead — read the papers

New hypotheses this failure suggests, each with a crucial experiment, a rival explanation of the original result, and the papers it rests on. Written by AI from paper titles and abstracts found on OpenAlex (and Europe PMC, for life and health sciences).

Related failures (1)

Matched on shared genes, mechanisms and ways of failing as well as wording. Each shows why it matched — treat these as leads rather than verdicts.

chronic lymphocytic leukemiaActivation-induced deaminase (AID)different research area
AID, which can remove DNA methylation, would change the methylation of disease-related genes in chronic lymphocytic leukemia cells and so change their expression.
After AID expression, only minor differences appeared at individual sites. There were no recurrent methylation changes at specific target sites and no change in global methylation.
Why it matched: similar wording · mechanism: Epigenetic regulation

Links in published research

Where this experiment's genes are known to matter outside its own research area, and the papers behind those links. Sources: Open Targets Platform and Europe PMC.