# Regulation of RNA polymerase II pausing and directionality by ATP-dependent chromatin remodelers

> **NIH NIH R01** · UNIVERSITY OF TX MD ANDERSON CAN CTR · 2020 · $440,000

## Abstract

Summary
 The objective is to study the function of the SWI/SNF ATP-dependent chromatin remodeling complex in
promoter proximal pausing of RNA polymerase II and determination of transcriptional directionality, key
regulatory steps in transcription important in development and diseases. In the last several years, researchers
have found that in mammals most genes have RNA polymerase (RNAP) II paused 25-60 nts from the
transcription start site and that transcription can resume once the appropriate signal is provided. Regulation of
promoter proximal pausing has been uncovered to be as crucial, or perhaps more, of a regulatory step in gene
expression than formation of the preinitiation complex. There is currently very little known about connections
between RNAPII pausing and ATP-dependent chromatin remodelers such as SWI/SNF, even though the
chromatin structure at the promoter region is known to be an important determining factor in RNAPII pausing.
Polymerase pausing is also connected to the occurrence of divergent transcription, another recent finding in
transcription. Most non-coding RNA comes from divergent or bidirectional transcription in which transcription
occurs upstream of the coding region in the anti-sense direction. Similar to RNAP II pausing the directionality of
transcription is a developmentally controlled process. Preliminary data shows SWI/SNF’s involvement in the
regulation of both of these processes and the goals of this proposal are to delineate the molecular means of
SWI/SNF regulation of these relatively new aspects of transcription.
 SWI/SNF is one of the most frequently mutated epigenetic factors in cancer, occurring in ~20% of all
cancers, and mutations in SWI/SNF are the molecular drivers for two neurological disorders, Nicolaides-Baraister
and Coffin-Siris syndromes. The SWI/SNF complex is also crucial for both pluripotency and differentiation. As a
master gatekeeper of chromatin, it has been assumed to be primarily involved in making DNA accessible for
formation of the transcription initiation complex. The premise of this proposal is that the functions of SWI/SNF in
regulation of RNAPII pausing and directionality is as vital for its role in development and human disease as
promoting formation of the transcription initiation complex. In addition, we will examine the important question
of how SWI/SNF regulates the synthesis of eRNAs, short RNAs transcribed at enhancer regions, given the
remarkable similarity with which both enhancers and promoters are transcribed, often bi-directionally, and using
the same transcription and elongation factors. eRNAs facilitate long-range interactions between promoters and
enhancers, and are synthesized prior to the synthesis of its corresponding coding RNAs. This proposal examines
how SWI/SNF influences RNAPII pausing and directionality at enhancer regions, which is likely to be important
for enhancer activity.

## Key facts

- **NIH application ID:** 9903395
- **Project number:** 5R01GM131639-02
- **Recipient organization:** UNIVERSITY OF TX MD ANDERSON CAN CTR
- **Principal Investigator:** Blaine Bartholomew
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $440,000
- **Award type:** 5
- **Project period:** 2019-04-15 → 2023-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9903395

## Citation

> US National Institutes of Health, RePORTER application 9903395, Regulation of RNA polymerase II pausing and directionality by ATP-dependent chromatin remodelers (5R01GM131639-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9903395. Licensed CC0.

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