# Analysis of chromatin-RNA interactions during the cell cycle.

> **NIH NIH R01** · BOSTON UNIVERSITY MEDICAL CAMPUS · 2022 · $330,000

## Abstract

DNA is packaged by histone proteins into chromatin in order to fit into the nucleus of a cell. Globally, chromatin
can be separated into open, transcriptionally active and closed, transcriptionally silent compartments. Many
different nonhistone, chromatin-binding proteins contribute to global chromatin structure. Chromatin remodeling
enzymes, transcription factors, and transcription-associated RNAs are important for decondensing
transcriptionally active portions of the genome. Heterochromatin proteins and associated noncoding RNAs are
important for condensation of the transcriptionally inactive portions of the genome. Changes in chromatin
organization and compaction are critical for cell state changes during development and chromosome
segregation during mitosis.
 Chromosome structure changes dramatically at the beginning of mitosis as chromosomes compact and
individualize in preparation for segregation. As cells enter into mitosis all of the structure present in the
interphase nucleus is erased. Erasure of interphase nuclear structure is correlated with the stepwise removal
of the Cohesin complex. Chromosome condensation and individualization are accomplished by the combined
action of the Condensin complexes and Topoisomeriase IIα. Interestingly, dramatic changes in chromosome
structure are temporally correlated with suppression of transcription. At the end of mitosis chromosomes
cluster and decondense to reform a single interphase nucleus. Chromosome decondensation and clustering is
accomplished by the rebinding of many different proteins that are removed from chromatin during mitosis and
is temporally correlated with the resumption of nuclear transcription.
 While changes in chromatin structure during mitosis are correlated with changes in nuclear
transcriptional activity, little is known about how the two processes are linked. We have recently discovered
that prophase removal of the Cohesin complex form chromosomes is critical for silencing mitotic transcription
and that removal of chromatin-bound RNAs from chromosomes during mitosis is mediated by phosphorylation
of SAF-A. The identification of molecular pathways linking changes in chromosome structure to changes in
transcriptional activity presents an opportunity to understand how these events are linked. In this proposal we
will reconstitute the biochemistry of nucleic acid interactions mediated by SAF-A to provide a picture of how
this abundant protein controls chromosome structure. We will then examine how removal of SAF-A from
chromatin promotes chromosome condensation during prophase. We will then examine how rebinding of SAF-
A to chromatin at the end of mitosis promotes nuclear reformation and transcriptional activation. Collectively,
the experiments outlined in this proposal will provide new insight into changes in chromatin-RNA interactions
that control chromatin structure and how these changes contribute to accurate chromosome segregation and
transcriptional regulation.

## Key facts

- **NIH application ID:** 10338329
- **Project number:** 1R01GM144352-01
- **Recipient organization:** BOSTON UNIVERSITY MEDICAL CAMPUS
- **Principal Investigator:** Michael Demian Blower
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $330,000
- **Award type:** 1
- **Project period:** 2022-03-16 → 2025-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10338329

## Citation

> US National Institutes of Health, RePORTER application 10338329, Analysis of chromatin-RNA interactions during the cell cycle. (1R01GM144352-01). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10338329. Licensed CC0.

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