# Mechanisms regulating lncRNA short and long range signaling

> **NIH NIH R01** · NORTHWESTERN UNIVERSITY · 2021 · $556,832

## Abstract

Major technological breakthroughs in biology reveal new dimensions in our
understanding of gene regulation and chromatin 3-D structure. At the heart of
understanding gene regulation are studies of transcription-regulating, long non-coding
RNAs (lncRNAs) that are transcribed from enhancers. While the concept that lncRNAs
play genome-wide roles as transcriptional regulators is now accepted, the relationship
between lncRNAs and chromatin 3-D structure is still unclear. Therefore, a central
question in biology remains: How do lncRNAs interact with chromatin to establish
gene regulatory networks in the context of chromatin 3-D structure?
 By using a combination of large-scale analyses, including next-generation
nucleic-acid sequencing, mass spectrometry protein sequencing, genome-wide
chromosome conformation, and bioinformatics, we can now investigate the relationship
between epigenetic factors, gene regulation, and chromatin 3-D structure.
 For over a decade, my lab has been studying transcriptional regulation by Evf2,
the first enhancer-regulating, ultraconserved lncRNA (Feng et al. 2006, Bond et al. 2009,
Berghoff et al. 2013, Cajigas et al. 2015). Collectively, these studies establish some
fundamental principles regarding the role of lncRNAs in gene regulation, including the
finding that a single developmentally regulated lncRNA controls GABAergic interneuron
development and adult brain circuitry (Bond et al. 2009). Our previous work focused on
Evf2 regulation of adjacent or overlapping, Dlx5/6 intergenic enhancers, and reported
short-range effects on gene expression, transcription factor recruitment, histone
modifications, site-specific CpG DNA methylation, and direct inhibition of ATPase and
chromatin remodeling activities (Bond et al. 2009, Berghoff et al. 2013, Cajigas et al.
2015).
 In this proposal, we will combine the genetic and biochemical tools developed in
my lab over the past decade, with recent large-scale technologies, to determine the
relationship between the Evf2 gene regulatory network and chromatin 3-D structure.

## Key facts

- **NIH application ID:** 10403749
- **Project number:** 7R01MH111267-05
- **Recipient organization:** NORTHWESTERN UNIVERSITY
- **Principal Investigator:** Jhumku Dutt Kohtz
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $556,832
- **Award type:** 7
- **Project period:** 2017-05-24 → 2024-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10403749

## Citation

> US National Institutes of Health, RePORTER application 10403749, Mechanisms regulating lncRNA short and long range signaling (7R01MH111267-05). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10403749. Licensed CC0.

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