# Deciphering the contribution of enhancer transcription to enhancer function

> **NIH NIH F31** · UNIVERSITY OF CALIFORNIA, SAN DIEGO · 2021 · $38,965

## Abstract

PROJECT SUMMARY/ABSTRACT
The applicant is requesting two years of support from a Ruth L. Kirschstein National Research Service Award
for Individual Predoctoral Fellowship to Promote Diversity in Health-Related Research (F31-Diversity) to examine
the relationship between enhancer transcription and enhancer function. Enhancers have been shown to initiate
short, non-coding transcripts in quantities rivaling promoters, yet their role on enhancer function remains
controversial. My preliminary data suggests that enhancers and promoters synchronize their activity to form co-
regulated domains. This result is surprising given that previous studies using total RNA measurements have
indicated that enhancer eRNAs ramp up before their associated mRNAs, suggesting that enhancers get
activated first and that this activation then gets transmitted to the associated promoters. Co-regulated domains
explain several of the mechanisms that the textbook model of enhancer function fails to. These include that
enhancer sequences are indistinguishable from promoters, that they are bound and initiate transcription by RNA
polymerase II, that enhancers and promoters form hubs in the nucleus, that enhancers act in an additive or
synergistic manner, and the redundancies observed when knocking out single enhancers in a multi-enhancer
locus. The goal of this research is to test the hypothesis that enhancers may function by serving as
simultaneously activated and mutually reinforcing transcription initiation sites within CRDs. This hypothesis
implies that enhancer transcription would be essential for enhancer function. I will test this hypothesis in three
specific aims: (1) determine the generality of enhancer-promoter co-regulatory domains across signaling
responses, to uncover whether the formation of co-regulated domains are a general regulatory mechanism
underlying signal response (2) determine the relationship between enhancer transcription and enhancer function
outside of their native genomic environment, to examine the relationship between enhancer transcription and
enhancer function outside of their native genomic context, and (3) determine the impact of silencing enhancer
transcription on gene activation in vivo, to determine the influence that shutting down enhancer transcription ahs
on enhancer function in its native genomic context. This training will allow me to (1) develop skills in the areas
of research design, analysis and interpretation using next-generation sequencing and molecular biology
techniques; (2) learn the fundamentals of molecular, chromatin, and enhancer biology; (3) successfully defend
a dissertation; and (4) obtain a competitive post-doctoral fellowship with the long-term goal to become a
successful, independently-funded scientist at a research-intensive university.

## Key facts

- **NIH application ID:** 10316087
- **Project number:** 1F31HG011823-01A1
- **Recipient organization:** UNIVERSITY OF CALIFORNIA, SAN DIEGO
- **Principal Investigator:** Carlos Guzman
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $38,965
- **Award type:** 1
- **Project period:** 2022-01-01 → 2023-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10316087

## Citation

> US National Institutes of Health, RePORTER application 10316087, Deciphering the contribution of enhancer transcription to enhancer function (1F31HG011823-01A1). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10316087. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*