# Mechanisms of enhancer-promoter communication, genome organization and transcription control

> **NIH NIH R01** · SLOAN-KETTERING INST CAN RESEARCH · 2022 · $484,290

## Abstract

ABSTRACT
Metazoan genomes achieve complex gene control by uncoupling regulatory DNA elements from target
promoters and allowing regulation at a distance. Thus, a gene can be differentially expressed in different cell
types and under different environmental signals or developmental cues. How distal regulatory elements
(enhancers) target specific gene promoters, how the search process is shaped by the topology of the genome
in the nucleus and how enhancer-promoter interactions are facilitated by regulatory complexes that relay
signals to the RNA Polymerase II and control transcription activity remains a mystery. Our goal is to
understand molecular and biophysical mechanisms that enable enhancer-promoter communication in human
and other mammalian cells. Towards these goals and during the period of this award we will accomplish the
following: (i) visualize the dynamic communication of enhancers and target promoters simultaneously with the
association of regulatory complexes and gene activity, using novel single-molecule and super-resolution
approaches for non-invasive 4D imaging of structure and function of the genome in single live cells; (ii)
determine mechanisms by which different classes of architectural proteins shape genome folding, enhancer-
promoter communication and transcription kinetics; (iii) dissect the function and interdependencies of individual
constituent enhancer elements within complex regulatory landscapes controlling cell identity genes. Our results
will establish quantitative frameworks for understanding the biochemistry of transcription regulation in the
crowded environment of the nucleus and for interpreting gene regulation and genome organization using soft-
matter/polymer physics and related biophysical concepts. These conceptual leaps are needed to ultimately
understand physical chromatin organization at sub-Mb scales, the scale most relevant for regulatory genome
interactions. Our integrated structure-function approach will provide functional validation and critical tests for
gene “regulation-at-a-distance” models. The proposed studies will not only provide substantial new knowledge
on the mechanisms of promoter-enhancer communication but will also set the stage for further studies of the
interplay of genome topology/organization and gene expression regulation.

## Key facts

- **NIH application ID:** 10343329
- **Project number:** 1R01GM144508-01
- **Recipient organization:** SLOAN-KETTERING INST CAN RESEARCH
- **Principal Investigator:** Alexandros Pertsinidis
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $484,290
- **Award type:** 1
- **Project period:** 2022-08-01 → 2026-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10343329

## Citation

> US National Institutes of Health, RePORTER application 10343329, Mechanisms of enhancer-promoter communication, genome organization and transcription control (1R01GM144508-01). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10343329. Licensed CC0.

---

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