# The effect of nucleosomes on the earliest stages of RNA polymerase II transcription

> **NIH NIH R01** · CLEVELAND CLINIC LERNER COM-CWRU · 2021 · $223,088

## Abstract

Project Summary
Appropriate control of gene expression is essential for correct cellular function and is disrupted
in many human diseases. RNA polymerase II (Pol II) is the engine of gene expression and the
target of regulation for almost every facet of its function. In the nucleus of the cell, Pol II is
recruited to promoters, locates transcription start sites, and enters into transcription in a
chromatin context. This occurs amidst flanking nucleosomes, which are the primary unit of
chromatin. It is clear that control of the earliest stages of transcription is a major aspect of gene
regulation in eukaryotes from simple yeast to humans. Genomic studies have suggested that
the encounter of Pol II with the first nucleosome immediately downstream of the promoter (the
+1 nucleosome) is important in this regulatory process, but the results of those studies are
correlations, based on averages of distributed populations. The significance of those
correlations is rarely tested by direct biochemical assays. This proposal will provide those tests
by adopting biochemical approaches developed in the Luse lab to directly address the functional
importance of the promoter proximal nucleosome for assembly of the Pol II transcription
complex and the initial transition into transcript elongation. We will also determine the
consequences for the +1 nucleosome resulting from the advance of the transcriptional
machinery. Our in vitro systems have the unique ability to reveal the fundamental nature of Pol
II/nucleosome interactions that additional factors can modulate or regulate. We will employ both
the human and yeast transcription systems. These are the best understood eukaryotic
transcription systems at the biochemical level and they provide complementary strengths for our
experiments. We will incorporate the full complexity of eukaryotic promoters (both containing
and lacking the TATA motif) in our work, which allows us to address the real possibility that the
response of Pol II to the +1 nucleosome depends on promoter architecture. We will build on the
extensive earlier studies by both investigators to begin testing proposed models of RNA
polymerase II-nucleosome interactions with approaches that lead to mechanistic conclusions.

## Key facts

- **NIH application ID:** 10236508
- **Project number:** 5R01GM121428-04
- **Recipient organization:** CLEVELAND CLINIC LERNER COM-CWRU
- **Principal Investigator:** Donal Luse
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $223,088
- **Award type:** 5
- **Project period:** 2018-09-01 → 2024-07-19

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10236508

## Citation

> US National Institutes of Health, RePORTER application 10236508, The effect of nucleosomes on the earliest stages of RNA polymerase II transcription (5R01GM121428-04). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10236508. Licensed CC0.

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