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Serge McGraw @sergemcgraw.bsky.social · 02/02/2026

Conserved promoter hypermethylation between mESCs and human cancers showed signs of epigenetic priming and had sex-specific effects. 7/9

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Serge McGraw @sergemcgraw.bsky.social · 02/02/2026

The same promoter regions hypermethylated by DNMT1 overexpression in mESCs are also hypermethylated in various human cancers — demonstrating the biological relevance and translational potential of this model. 6/9

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Serge McGraw @sergemcgraw.bsky.social · 02/02/2026

DNMT1-targeted cancer therapies may have limits: some hypermethylation in mESCs resisted erasure following acute DNMT1 depletion. 5/9

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Serge McGraw @sergemcgraw.bsky.social · 02/02/2026

We also found increased CpG‑to‑CpG methylation variability, a feature associated with epigenetic instability in cancer. DNMT1 excess didn’t just shift DNA methylation levels — it disrupted DNA methylation precision. 4/9

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Serge McGraw @sergemcgraw.bsky.social · 02/02/2026

Despite global hypomethylation, we observed focal hypermethylation at promoters and CpG islands — another hallmark of cancer methylomes. These promoter DMRs were linked to pathways that align with the vast pathological potential of DNMT1 overexpression. 3/9

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Serge McGraw @sergemcgraw.bsky.social · 02/02/2026

Despite DNMT1 being a maintenance methyltransferase, overexpression led to global, widespread hypomethylation in mESCs, mirroring a paradox seen in cancer. 2/9

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Serge McGraw @sergemcgraw.bsky.social · 27/02/2025

The timing of the rescue intervention was critical for embryoid body differentiation. Early rescue in mESCs led to better outcomes, while delaying it until after differentiation initiation intensely worsened molecular and cellular effects.

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Serge McGraw @sergemcgraw.bsky.social · 27/02/2025

Signs of genomic instability were detected, along with morphological and functional responses.

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Serge McGraw @sergemcgraw.bsky.social · 27/02/2025

Transposable elements became permanently de-repressed, with evidence of potential novel chimeric transcripts being generated.

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Serge McGraw @sergemcgraw.bsky.social · 27/02/2025

Analyzing the impact on known imprinted regions and their unique properties enabled the discovery of 20 regions with imprinted-like epigenetic and regulatory signatures.

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Serge McGraw @sergemcgraw.bsky.social · 27/02/2025

Transient loss of DNMT1 profoundly impacted multiple layers of epigenetic regulation, including DNA methylation, five key histone modifications, and gene expression.

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Serge McGraw @sergemcgraw.bsky.social · 27/02/2025

Using mESCs, we showed that rescuing DNMT1 failed to fully reverse the repercussions of its loss on a broad molecular and functional scale. Only partial reversal could be achieved; many effects were permanent, and some arose from the rescue intervention itself.

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Serge McGraw @sergemcgraw.bsky.social · 24/12/2024

Merry Christmas and happy holidays everyone!

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Serge McGraw @sergemcgraw.bsky.social · 20/12/2024

Secret Santa with a twist…people can steal my gift if people get me to say one of my favourite words…

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Serge McGraw @sergemcgraw.bsky.social · 15/12/2024

Thank you Belize! ☀️🌊🏝️🐚🐠 I had a blast. Now back to Montreal ❄️🥶

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Serge McGraw @sergemcgraw.bsky.social · 05/12/2024

Random texts, emails and slack messages from lab folks of data makes my day, and gets me excited for our next lab meetings! Like this one just received. Cell phone snap shot of immunostaining of iPSC-derived cortical #organoid!

Image from immunostaining of iPSC-derived cortical #organoid!

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