# Mechanisms Underlying Enhancer Rnp Mediated Gene Regulation And Genome Organization

> **NIH NIH R01** · UNIVERSITY OF TEXAS HLTH SCI CTR HOUSTON · 2021 · $357,741

## Abstract

PROJECT ABSTRACT
Enhancers play critical roles in determining lineage-specific gene expression and cellular identities, and are
enriched in noncoding disease mutations and risk loci. There is an urgent need to elucidate the complete
mechanisms of enhancer functions and malfunctions to better understand disease etiology and to develop new,
enhancer-targeting therapies. The recent finding that active enhancers often generate noncoding enhancer
RNAs (eRNAs) has provided a new perspective to interpret enhancer activity in the context of RNA-mediated
regulation. This proposal aims to establish a unique research direction by developing new approaches to
address the molecular mechanisms underlying eRNA functions in gene/genome regulation. Our overall
hypothesis is that eRNAs assemble specific ribonucleoprotein complexes (RNPs) to organize high-order
enhancer structures in the three-dimensional nucleus to control gene transcription. We have three specific
aims in this proposal. We plan to use a robust RNA capture method that we have developed to systematically
identify eRNA:protein interactomes in human cells. For the first aim, we plan to focus on two novel eRNA-
binding proteins (eRBPs) to characterize their functions in gene transcription and 3D genome interaction in
mammalian cells. Subsequently, we have two aims to study the mechanisms of each of the two eRBPs to fully
characterize the biochemical basis permitting eRNA:protein interaction and their possible involvement in
mediating the formation of transcriptionally-associated sub-nuclear condensates. The expected results from
this proposal will provide novel mechanistic insights into gene transcriptional regulation and RNA functions in
mammalian cells. As enhancers become important drivers in disease development, these mechanistic insights
may offer new therapeutic strategies to treat enhancer-driven diseases.

## Key facts

- **NIH application ID:** 10260610
- **Project number:** 5R01GM136922-02
- **Recipient organization:** UNIVERSITY OF TEXAS HLTH SCI CTR HOUSTON
- **Principal Investigator:** Wenbo Li
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $357,741
- **Award type:** 5
- **Project period:** 2020-09-10 → 2025-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10260610

## Citation

> US National Institutes of Health, RePORTER application 10260610, Mechanisms Underlying Enhancer Rnp Mediated Gene Regulation And Genome Organization (5R01GM136922-02). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10260610. Licensed CC0.

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