# Chemical strategies to investigate biochemical crosstalk in human chromatin

> **NIH NIH R35** · UNIVERSITY OF WASHINGTON · 2024 · $366,279

## Abstract

PROJECT SUMMARY
 Chromatin is a massive nucleoprotein complex that packages about three billion
base pairs of genetic information in nucleated cells. Histones and transcription factors
(TFs) are two important families of proteins associated with chromatin that play key
roles in organizing, protecting and activating our genes. A conserved feature among
histones and TFs is the critical role that post-translational modifications (PTMs) play in
controlling their diverse functions. Many gaps remain in our understanding of the
mechanistic roles for specific histone and TF PTMs that are either low in abundance
or where the necessary molecular biological and chemical tools are unavailable for
mechanistic studies. This is especially challenging when studying regulation of the
tumor suppressor p53 that is rapidly turned over by the proteasomal machinery in our
cells. The proposed research project seeks to overcome challenges arising from the
low abundance and heterogeneity of histone and p53 modifications by applying a
combination of chemical and molecular biological tools to generate site-specifically
modified proteins. Specifically, sumoylated histones H2B and H4 and methylated p53
will be generated by new protein semisynthesis techniques. The semisynthetic
proteins will be subjected to a range of biophysical and biochemical assays in order to
elucidate the mechanistic roles for sumoylation and methylation in regulating chromatin
structure and function. Results from biochemical assays will be further validated in cell-
based studies to arrive at a complete picture of the molecular mechanisms underlying
gene regulation by histone sumoylation and p53 methylation. The long-term goal of
this project is to identify new biochemical relationships, or crosstalk, in cellular
chromatin that may be controlled to engineer cellular fates and selectively
therapeutically targeted in human diseases.

## Key facts

- **NIH application ID:** 10833611
- **Project number:** 5R35GM149228-02
- **Recipient organization:** UNIVERSITY OF WASHINGTON
- **Principal Investigator:** Champak Chatterjee
- **Activity code:** R35 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $366,279
- **Award type:** 5
- **Project period:** 2023-05-01 → 2028-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10833611

## Citation

> US National Institutes of Health, RePORTER application 10833611, Chemical strategies to investigate biochemical crosstalk in human chromatin (5R35GM149228-02). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10833611. Licensed CC0.

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