# Mechanistic dissection of dynamics of transcriptional regulation by chromatin looping

> **NIH NIH F32** · MASSACHUSETTS INSTITUTE OF TECHNOLOGY · 2021 · $65,994

## Abstract

A major driver of transcriptional regulation in mammals is the association of gene promoters with
enhancers, which can be hundreds of kilobases away from their cognate promoters. Enhancers have been
proposed to potentiate transcription through looping to contact the promoter. The broader 3D organization of the
genome into topologically associated domains (TADs) has been proposed to restrict E-P looping to primarily
occur inside the same TAD and not between two TADs, and to thereby contribute to regulation of transcription.
Both TAD structure and enhancer activities change through development, and mutations of many of the factors
involved in regulating genome organization have been identified as causative features of both developmental
disease and cancers. However, recent studies of developmental genes have obtained conflicting results on
whether genome organization can influence transcription. Furthermore, it remains unclear as to how E-P
interactions are related to transcription, and whether direct contact is even required.
 The majority of studies of 3D genome organization and chromatin looping have employed genomics or
microscopy approaches which rely on fixation, and therefore do not allow for the measurement of the dynamics
of these processes. Additionally, most recent studies have focused on single, developmentally regulated genes
which may be subject to a high degree of redundancy and complexity. Therefore, in order to address these major
questions of the contribution of TADs and E-P contact to transcriptional regulation, the proposed research will
employ a bottom-up approach to construct synthetic TADs and E-P pairs, and measure chromatin looping and
transcription dynamics together in live cells through newly developed live-cell super resolution microscopy
approaches. Mechanistic hypotheses for the function of these processes will then be developed using polymer
simulations of loop extrusion and evaluated through comparison with experimental data and targeted
perturbations without the redundancy and complexity inherent to endogenous genes. Together, the proposed
research will uncover the interplay between genome organization and transcriptional regulation and develop a
mechanistic understanding of both TAD formation and E-P interactions. This will provide a basis for future
development of approaches to correct misfolding of the genome in disease.
 The proposed research will be paired with training to develop the applicant's skills as a research scientist
to allow him to succeed in the proposed project and in his future career as he aims to become an independent
PI. In addition to developing the applicant's experimental and computational expertise, mentorship from the
sponsor and co-sponsor will involve training in communicating the applicant's research, mentorship of students,
lab management, responsible conduct of research and preparation for future career goals. This training will be
conducted in a leading academic environment in MIT's ...

## Key facts

- **NIH application ID:** 10313180
- **Project number:** 1F32GM140548-01A1
- **Recipient organization:** MASSACHUSETTS INSTITUTE OF TECHNOLOGY
- **Principal Investigator:** Miles Kocur Huseyin
- **Activity code:** F32 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $65,994
- **Award type:** 1
- **Project period:** 2021-09-30 → 2024-09-29

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10313180

## Citation

> US National Institutes of Health, RePORTER application 10313180, Mechanistic dissection of dynamics of transcriptional regulation by chromatin looping (1F32GM140548-01A1). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10313180. Licensed CC0.

---

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