# An inquiry into the function of Ronin in embryogenesis and pluripotent stem cells

> **NIH NIH R01** · ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI · 2021 · $466,125

## Abstract

PROJECT SUMMARY
A long-held view is that gene regulatory complexity in stem cells and development is achieved through the
judicious organization of millions of enhancer elements. A recently identified new class of DNA binding fac-
tors called THAPs (Thanatos-associated domain-containing apoptosis-associated proteins) may provide new
insights into gene regulation in stem cells. One key member of this family, Ronin (Thap11), was discovered by us
in embryonic stem cells. Ronin is expressed during the earliest stages of embryonic development and is essential
for the maintenance of stem cell pluripotency, both in vitro and in vivo. Since Ronin lacks appreciable transac-
tivation activity but functions as a DNA-binding nuclear protein with strong protein dimerization activity, we
considered that it may not act in the classical manner of a transcriptional regulator (e.g., having an acidic activa-
tion domain) but instead might augment gene expression by facilitating communication among Ronin binding
sites through DNA looping. This working hypothesis gained traction when we found that most (83%) of the
looping events mediated by Ronin involve promoter-to-promoter links rather than the enhancer-to-promoter
interactions seen with typical transcription factors. In this research study we will (i) establish the effects of Ro-
nin-mediated promoter tethering on transcription and gene regulation in stem cells; (ii) determine the influence
of promoter tethering on developmental transitions especially from the naïve to primed pluripotent state; and
(iii) ask if other THAPs participate in development specific gene clustering as well.

## Key facts

- **NIH application ID:** 10134366
- **Project number:** 5R01GM129329-04
- **Recipient organization:** ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI
- **Principal Investigator:** Thomas P. Zwaka
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $466,125
- **Award type:** 5
- **Project period:** 2018-07-11 → 2023-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10134366

## Citation

> US National Institutes of Health, RePORTER application 10134366, An inquiry into the function of Ronin in embryogenesis and pluripotent stem cells (5R01GM129329-04). Retrieved via AI Analytics 2026-05-21 from https://api.ai-analytics.org/grant/nih/10134366. Licensed CC0.

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