# Defining the mechanisms of epigenetic information flow

> **NIH NIH R35** · UNIVERSITY OF CHICAGO · 2024 · $56,817

## Abstract

Project Summary
Chromatin, the assemblage of protein, DNA and RNA that represents the physiologic form of the
eukaryotic genome, imposes a million-fold length-scale compaction to fit DNA in the nucleus.
Rather than serving as mere static packaging, chromatin structure acts as a dynamic regulator
of underlying DNA function. Local chromatin structure may be stable for decades, yet is
sufficiently dynamic to respond to signaling pathways, potentiating transcriptional program
changes in development, disease, and environmental changes. Indeed, cellular identity and
changes thereof are intimately connected to chromatin states-- keeping a neuron a neuron and
not a liver cell. Apart from DNA sequence-specific transcription factors, the information carriers
responsible for this structural variation are chemical modifications to the genome itself and
attendant histone proteins involved in packaging (often referred to as “epigenetic” marks), as
well as noncoding RNA acting at the chromatin interface. Although little known about these
epigenetic information carriers, it is clear that they play crucial roles in development, cognition
and disease. Elucidation of the molecular mechanisms by which epigenetic information carriers
impact chromatin structure and function, particularly in the context of transcriptional activation is
the unifying theme of the Ruthenburg lab. In the next four years, we will discover and
characterize the detailed mechanisms of new epigenetic information carriers, focusing on
nucleosome-level variation and orphaned histone modifications, defining binding partners for
recently appreciated DNA modifications and their function, and performing detailed mechanistic
characterization of a class of molecules we discovered--chromatin-enriched noncoding RNA that
act as local transcriptional activators. In addition, we will biochemically define the function of
RNA in the MLL/SET1 family of histone modification complexes and its functional consequences
in cellular contexts. Our interdisciplinary work in these areas will require the development of new
tools and experimental approaches—our outstanding track record of pioneering tool
development with NIGMS funding makes the case that future efforts will meet with similar
success. The fundamental mechanistic understanding of epigenetic information systems we will
develop through these avenues will impact our understanding of nuclear function and its
dysregulation in disease.

## Key facts

- **NIH application ID:** 11037206
- **Project number:** 3R35GM145373-02S1
- **Recipient organization:** UNIVERSITY OF CHICAGO
- **Principal Investigator:** Alexander Jackson Ruthenburg
- **Activity code:** R35 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $56,817
- **Award type:** 3
- **Project period:** 2022-09-08 → 2027-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/11037206

## Citation

> US National Institutes of Health, RePORTER application 11037206, Defining the mechanisms of epigenetic information flow (3R35GM145373-02S1). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/11037206. Licensed CC0.

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