# Mechanisms of chromatin remodeling at RNA polymerase II promoters

> **NIH NIH R01** · STATE UNIVERSITY NEW YORK STONY BROOK · 2021 · $332,233

## Abstract

7. PROJECT SUMMARY/ABSTRACT
 A fundamental aspect of all biological processes is gene expression, which is controlled at a variety of
levels, the first step being transcription. Transcription is regulated not only by sequence-specific factors such
as activators and repressors, but also by the underlying chromatin structure of the chromosomal DNA. This
structure is determined by various chromatin remodeling pathways. Genes encoding regulators of chromatin
remodeling pathways are frequently mutated in human cancers. Perturbation of chromatin regulators promotes
cancer progression in part by reverting the `on' or `off' chromatin states committed during tissue development
to a poised, stem-like state, thereby increasing gene expression plasticity that enables cancer cells to evolve
and adapt. Histone H2A.Z is an important chromatin regulator that poises genes for transcription. It is inserted
into nucleosomes immediately downstream of the promoters of most genes. Hyper-accumulation of H2A.Z
makes cancer cells more invasive and is linked with poor prognosis in cancer patients.
 Using the budding yeast model system, I previously demonstrated that the highly conserved, ATP-
dependent remodeler SWR replaces nucleosomal H2A with H2A.Z in a unidirectional manner in vitro. During
the current funding period, my lab found that H2A.Z is subjected to rapid turnover at both actively and
infrequently transcribed genes and that the transcription machinery targets H2A.Z nucleosomes for
disassembly in vivo. In addition, we developed a novel method for globally determining the levels of H2A.Z and
H2A-containing nucleosomes in yeast and human cells called VivosX. This proposal will extend this work to (1)
dissect the molecular mechanisms by which the SWR chromatin remodeling enzyme inserts H2A.Z into
specific sites on chromatin and (2) elucidate the molecular events at promoters after H2A.Z insertion. This
knowledge may ultimately reveal molecular targets for drugs that can counteract the aberrant levels of H2A.Z
in cancer cells.

## Key facts

- **NIH application ID:** 10105201
- **Project number:** 5R01GM104111-08
- **Recipient organization:** STATE UNIVERSITY NEW YORK STONY BROOK
- **Principal Investigator:** Edward E Luk
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $332,233
- **Award type:** 5
- **Project period:** 2013-09-01 → 2023-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10105201

## Citation

> US National Institutes of Health, RePORTER application 10105201, Mechanisms of chromatin remodeling at RNA polymerase II promoters (5R01GM104111-08). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10105201. Licensed CC0.

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