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Excited to share our new preprint!
We uncover a new layer of control in how cells restart transcription after mitosis.
👉 TTF2 prevents premature rRNA transcription during mitotic exit (https://t.co/LgfirEoKEw)
🧵1/
Excited to share our new preprint!
We uncover a new layer of control in how cells restart transcription after mitosis.
👉 TTF2 prevents premature rRNA transcription during mitotic exit (https://t.co/LgfirEoKEw)
10/
Our work links two fields that often don’t talk enough:
🧬 Mitosis
🧬Transcription regulation
and highlights how their coordination preserves cellular integrity
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Importantly, this challenges the idea that transcription simply resumes passively as cells exit mitosis.
Instead, reactivation is actively restrained and timed
5/
As expected:
Loss of TTF2 → retention of chromatin-associated transcripts in metaphase
(mainly RNA Pol II–derived)
✔️ Consistent with its known role in transcriptional clearance
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Using nascent RNA labeling + polymerase-specific perturbations,
we tracked transcription dynamics across mitosis in:
• human embryonic stem cells
• HeLa cells
3/
We focused on TTF2, a factor known to remove RNA Polymerase II transcripts at mitotic entry.
But what happens later—during transcriptional reactivation?
2/
During mitosis, transcription is globally shut down.
As cells exit mitosis, transcription must be reactivated—precisely and in the right order.
How this timing is controlled remains poorly understood.
5/ This means that mitotic transcription isn’t just a passive consequence of cell cycle stage — it actively threatens genome stability when not properly regulated.
4/ The result? When transcription isn’t cleared, sister chromatid resolution is impaired — a critical step needed to ensure faithful chromosome segregation in anaphase.
3/ Importantly, we show that these defects arise because R-loops form when transcription persists during mitosis — and preventing transcription reverts the defects. That establishes a causal link.
2/ Using TTF2 depletion to force nascent transcripts to persist on mitotic chromatin, we found that this abnormal retention leads to mitotic errors including abnormal chromosomes and bridges.
1/ During mitosis, cells globally suppress transcription as chromosomes condense — a conserved hallmark of cell division. But what if this repression fails? 😮💨