# Chromatin of repetitive elements

> **NIH NIH R01** · ST. JUDE CHILDREN'S RESEARCH HOSPITAL · 2021 · $359,000

## Abstract

Summary
Silencing of transposable and repetitive elements maintains genome integrity, and defects in silencing
pathways lead to cancer formation. Despite the importance, little is known how transposable and repetitive
elements are initially recognized and targeted for silencing and how they regulate important biological
processes. To address this knowledge gap, we will combine genetics and molecular biology with
biochemistry and cryo-EM.
Genomes are under constant threat of invasion by transposable elements and other genomic parasites.
These foreign genomic elements will use the host for their own expression and proliferation. Silencing of
existing transposable and repetitive elements has been well studied, however, little is known how new
transposable elements are recognized. Although most of the repetitive genome consist of transposable and
other foreign elements, repeats of ribosomal DNA (rDNA) form a unique type of a repetitive genome, in
which some repeats are silenced while others are highly expressed. rDNA is localized in the nucleolus, a
special compartment that is considered to be phase separated by nucleophosmin and fibrillarin, and where
ribosome assembly occurs. Despite the importance of the rDNA locus, it is largely unknown how chromatin
structure at rDNA is regulated. The major goals of the proposed research is to determine how new
transposable elements are recognized and how and why chromatin regulates sorting and separation of
nascent ribosomes.
Guided by the strong preliminary data, we propose to pursue two Specific Aims to understand biology of
repetitive elements. We will determine what features in invasion of new transposable elements are
recognized by the host and which host machineries can discover those elements (Aim
1). Moreover, we will combine cryo-EM with biochemistry and genetics to determine the role of
chromatin in ribosome biogenesis (Aim 2).
Together, our proposed studies will have broad impact in chromatin field by showing how chromatin
regulates ribosome biogenesis and how insertions of new transposons are recognized by the host. Our
long-term goals are to understand the regulation of genome expression by chromatin and discover why
mutations in chromatin proteins lead to the formation of cancer cells.

## Key facts

- **NIH application ID:** 10185471
- **Project number:** 1R01GM141694-01
- **Recipient organization:** ST. JUDE CHILDREN'S RESEARCH HOSPITAL
- **Principal Investigator:** Mario Halic
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $359,000
- **Award type:** 1
- **Project period:** 2021-04-01 → 2025-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10185471

## Citation

> US National Institutes of Health, RePORTER application 10185471, Chromatin of repetitive elements (1R01GM141694-01). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10185471. Licensed CC0.

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