# Regulation of Nuclear Functions by Drosophila Linker Histone H1

> **NIH NIH R01** · ALBERT EINSTEIN COLLEGE OF MEDICINE · 2020 · $379,052

## Abstract

The goal of this proposal is to elucidate molecular mechanisms by which H1 linker histone regulates
chromatin structure and activity. H1 and the four core histones (H2A, H2B, H3 and H4) are essential structural
proteins of metazoan chromosomes. Much of our knowledge about H1's roles in chromatin is derived from in
vitro studies, whereas our understanding of its functions in vivo remains very incomplete. We propose to use
the fruit fly, Drosophila melanogaster, as a model system because it provides many advantages for studies of
chromosome structure and genetic activity and because Drosophila H1 strongly resembles mammalian H1
linker histones.
 We developed an RNA interference (RNAi) approach to deplete Drosophila H1 nearly completely in vivo.
Using this approach, we showed that H1 is essential for Drosophila development and for normal chromosome
architecture. We also discovered that, in addition to its important structural role in chromatin, H1 plays an
active role in regulating epigenetic marking and silencing of heterochromatin by directly interacting with and
helping to recruit a core histone - modifying enzyme to chromatin. We also found that H1 has a role in
controlling DNA replication of polytene chromsomes. To gain a deeper understanding of the molecular
mechanisms by which H1 controls nuclear functions, we propose to: (1) Characterize the functional role of H1
in regulating DNA replication; (2) Understand how H1 interfaces with core histone posttranslational
modifications in chromatin; (3) Determine the contributions of H1 structural domains and post-translational
modifications to its biological functions. The successful completion of this project will help define the
mechanisms by which this major constituent of chromosomes partners with other cellular factors to regulate
the structure and activity of chromatin.

## Key facts

- **NIH application ID:** 9936211
- **Project number:** 5R01GM129244-04
- **Recipient organization:** ALBERT EINSTEIN COLLEGE OF MEDICINE
- **Principal Investigator:** DMITRY V FYODOROV
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $379,052
- **Award type:** 5
- **Project period:** 2018-08-01 → 2022-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9936211

## Citation

> US National Institutes of Health, RePORTER application 9936211, Regulation of Nuclear Functions by Drosophila Linker Histone H1 (5R01GM129244-04). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9936211. Licensed CC0.

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