# Histone chaperone networks for new and evicted histones

> **NIH NIH R01** · NORTHWESTERN UNIVERSITY · 2024 · $192,568

## Abstract

Project Summary
Nuclear DNA is packaged into nucleosomes by histone proteins to create chromatin.
The assembly of chromatin is not a passive process but requires the activity of a
network of histone-chaperone proteins that facilitate histone stability, prevent
aggregation, organize histone transport and facilitate their deposition. Histone
chaperones must deal with new histones, and also with pre-existing histones that
are evicted from chromatin. DNA replication, DNA transcription and access to other
control elements in the genome require nucleosomes be either moved out of the way
(slid) or removed, resulting in the eviction of pre-existing histones. Specific chaperones
contribute to the selective timing and placement of histone H3 variant deposition.
However, many histone chaperones are agnostic about the variant or modification
status of the histones they bind. Very little information exists as to how the chaperone
pathways for new and pre-existing histone differ. NASP has long been appreciated as a
key histone chaperone for histone H3 and histone H4, that functions irrespective of
histone variant or posttranslational modification. NASP also binds the histone
acetyltransferase enzyme HAT1 which contribute to the acetylation of new H4
histones at K12. Aim1 of this application will define novel interactions of NASP during
DNA synthesis that contribute to new histone supply. Our work will also take an
unbiased approach to ordering the process of histone-chaperone interaction during
new histone deposition and histone eviction. A novel chaperone pathway for pre-
existing nucleosomes that have been evicted from chromatin will be defined in aim 2 of
the proposal. Finally, Aim 3 will define a novel mechanism for crosstalk between
histone supply and nucleotide metabolism. Our work proposed in this application will
define, for the first time, differential processes that regulate fate of new and pre-existing
histones and provide a new paradigm for coordinated metabolic control.

## Key facts

- **NIH application ID:** 11098262
- **Project number:** 3R01GM143638-04S1
- **Recipient organization:** NORTHWESTERN UNIVERSITY
- **Principal Investigator:** Daniel Richard Foltz
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $192,568
- **Award type:** 3
- **Project period:** 2021-08-01 → 2025-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/11098262

## Citation

> US National Institutes of Health, RePORTER application 11098262, Histone chaperone networks for new and evicted histones (3R01GM143638-04S1). Retrieved via AI Analytics 2026-06-12 from https://api.ai-analytics.org/grant/nih/11098262. Licensed CC0.

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