# Dynamic regulation of chromatin by histone phosphorylation

> **NIH NIH R01** · ROCKEFELLER UNIVERSITY · 2021 · $423,750

## Abstract

Project Summary
In response to environmental cues, cells must selectively, rapidly, and robustly induce expression of specific
genes in the context of two meters of “chromatinized” DNA compacted within a complex, nuclear environment.
Chromatin is composed of nucleosomes, or repeated units of DNA bound to an octamer of histone proteins,
and chromatin is dynamically regulated by post-translational modifications to histones, chromatin modifying
enzymes, and transcription factors. Important for moving towards a more complete understanding of chromatin
regulation in the nuclear context, the recent description of extensive higher-order chromatin organization, and
assays to resolve this at a genomic level, enables the study of chromatin architecture during these
environmental responses. Key to this process of rapid and precise regulation of gene expression is what we
will call “signaling-to-chromatin” pathways, in which extracellular information is transmitted via kinase signaling
cascades to select chromatin regions resulting in local transcription factor activity, alterations in chromatin state
and structure, and transcription. However, surprisingly little is known of how activation of kinase cascades
transmits information directly to histones for dynamic regulation of chromatin architecture and characteristics to
affect transcription. We propose that the phosphorylation of both chromatin and transcription factors, and the
downstream effects of these phosphorylation events (e.g. regulation of “readers” and “writers” of chromatin)
may represent a rapid means of augmenting stimulation-induced transcription. Further elucidation of the role of
histone phosphorylation and the role of chromatin-associated kinases is the subject of this proposal.
Specifically, we will explore the role of H3S28 phosphorylation on chromatin architecture and accessibility (Aim
1), characterize the mechanism by which stimulation-induced H3.3S31 phosphorylation affects transcription
(Aim 2a/b), and uncover signaling-to-chromatin events during the immune response by investigating a
H3.3S31 kinase (Aim 2c). Importantly, the scope of transcription of inflammatory genes is critical to host
survival during pathogen infection and, therefore, we propose that these selectively employed mechanisms for
augmented transcription (e.g. coordinate regulation of transcription factors and chromatin by mitogen- and
stress-activated protein kinases (MSKs) and additional kinases identified in this proposal) represent essential
adaptations in response to pathogen pressure and are co-opted for diverse use in complex organisms. This is
highlighted by the fact that these signaling pathways we propose to study are also relevant to many human
diseases, including cancer. Utilizing our robust model system to uncover properties of chromatin regulation in
response to external signals, our findings could provide insight into fundamental biological processes, disease
mechanisms, and the therapeutic potential of...

## Key facts

- **NIH application ID:** 10124399
- **Project number:** 5R01GM040922-35
- **Recipient organization:** ROCKEFELLER UNIVERSITY
- **Principal Investigator:** CHARLES DAVID ALLIS
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $423,750
- **Award type:** 5
- **Project period:** 1990-07-01 → 2023-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10124399

## Citation

> US National Institutes of Health, RePORTER application 10124399, Dynamic regulation of chromatin by histone phosphorylation (5R01GM040922-35). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10124399. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*