# Histone Tall Interactions and Functions in Chromatin

> **NIH NIH R01** · UNIVERSITY OF ROCHESTER · 2020 · $336,026

## Abstract

Project Summary/Abstract:
The chromosomes of humans and other eukaryotes provide the seemingly contrasting functions of compacting
the genomic DNA several thousand times its length while also allowing for efficient processes such as
replicating the genome and expressing genes encoded within. To accomplish this, the DNA is assembled into
a complicated, multifaceted complex known as chromatin. The packaging of genome DNA into chromatin first
involves wrapping short (~200 bp) segments around protein spools comprised of histone proteins into
structures known as nucleosomes. Immensely long, genome-sized strings of nucleosomes are folded and
assembled into a hierarchy of structures of complex structures, to form chromosomes. Formation of these
large condensed structures involves essential inter-nucleosome interactions provided by the `tail' domains of
the core histone proteins, which protrude out from the main body of nucleosomes as well as binding of an
additional `linker' histone, which stabilizes higher order structures. Regulation of inter-nucleosome interactions
by posttranslational modifications within the core histone tail domains and linker histones is a key component
of the regulation of gene expression. While much is know about the structure of individual nucleosomes,
higher-order chromatin structures and inter-nucleosome interactions remain poorly defined. Moreover, how
posttranslational modifications within the histones modulate chromatin higher order structures to regulate gene
expression is not well understood. Importantly, mutations that alter histone posttranslational modifications have
been linked to diseases including cancers in humans. In prior work we documented inter-nucleosome
interactions in higher-order chromatin structures and defined critical aspects of how linker histones bind to
nucleosomes in chromatin. The primary goals of the work described in this proposal are to: 1) define impact of
modifications that transition inactive chromatin structures to those hospitable to active genes in a model
chromatin system; 2) define aspects of how linker histones bind to nucleosomes and oligonucleosome arrays,
and; 3) investigate newly discovered communication between the core histone tail domains, the architectural
proteins HMGN1 and HMGN2, and linker histones. In addition we will determine the molecular basis for our
newly discovered effect of H1 phosphorylation on H1 CTD structure and determine if there is a corresponding
effect on chromatin folding/compaction. We will use several novel approaches including site-directed
crosslinking of tail-DNA interactions, fluorescence and FRET based methods, and novel chemical probing
approaches to investigate structures and interactions in chromatin. These results will provide a basis for
understanding how transcription, replication, DNA repair, and other processes occur in a chromatin
environment.

## Key facts

- **NIH application ID:** 9851746
- **Project number:** 5R01GM052426-24
- **Recipient organization:** UNIVERSITY OF ROCHESTER
- **Principal Investigator:** Jeffrey J Hayes
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $336,026
- **Award type:** 5
- **Project period:** 1995-05-01 → 2022-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9851746

## Citation

> US National Institutes of Health, RePORTER application 9851746, Histone Tall Interactions and Functions in Chromatin (5R01GM052426-24). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9851746. Licensed CC0.

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