# Transcriptome regulation during mitosis

> **NIH NIH R01** · MASSACHUSETTS GENERAL HOSPITAL · 2020 · $43,529

## Abstract

Project Summary
Accurate chromosome segregation during mitosis and meiosis is critical for viability and
development. Errors in chromosome segregation lead to aneuploidy, which is closely correlated
with cancer. In order to ensure accurate chromosome segregation duplicated sister chromatids
must be dramatically condensed and individualized upon entry into mitosis. Accurate
chromosome distribution during mitosis depends on the interaction of duplicated sister
chromatids with the microtubules of the mitotic spindle. Each chromosome contains one
centromere that serves as the site for the formation of the kinetochore. At nuclear envelope
breakdown, proteins important for kinetochore:microtubule (K:MT) attachment and signaling
molecules that monitor K:MT attachment are recruited to the kinetochore. Successful
completion of cell division requires the coordinated regulation of centromere/kinetochore
assembly, kinetochore:microtubule attachment and chromosome condensation.
 Decades of work have identified hundreds of proteins that regulate various aspects of
mitosis. However, very little is known about regulation of the transcriptome during mitosis.
Recent work has demonstrated that remodeling of the transcriptome plays an important role in
mitotic regulation. This proposal will study two fundamental aspects of transcriptome remodeling
during mitosis. First, during mitosis, the majority of nuclear transcription is blocked, however,
centromeres escape transcriptional down-regulation. Surprisingly, very little is known about the
mechanism of transcriptional inhibition during mitosis or how disruption of mitotic transcriptional
inhibition impacts the fidelity of chromosome segregation. It is also unknown if the process of
mitotic transcriptional inhibition contributes to changing gene expression patterns. Second,
during interphase hundreds to thousands of RNAs are retained in the nucleus where they bind
to chromatin and regulate nuclear organization and gene expression. During mitosis many
nuclear RNAs are released from chromatin, yet little is known about the mechanism of RNA
removal from chromatin during mitosis. Additionally, it is unknown how disruption of RNA
release from chromatin impacts the process of chromosome segregation or gene expression
following mitosis. Our work will investigate how the transcriptome is remodeled during mitosis
and how this contributes to accurate chromosome segregation.

## Key facts

- **NIH application ID:** 9884164
- **Project number:** 2R01GM122893-03
- **Recipient organization:** MASSACHUSETTS GENERAL HOSPITAL
- **Principal Investigator:** Michael Demian Blower
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $43,529
- **Award type:** 2
- **Project period:** 2017-09-01 → 2020-06-01

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9884164

## Citation

> US National Institutes of Health, RePORTER application 9884164, Transcriptome regulation during mitosis (2R01GM122893-03). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9884164. Licensed CC0.

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