# Role of S-nitrosylation in Transdifferentiation

> **NIH NIH R01** · METHODIST HOSPITAL RESEARCH INSTITUTE · 2020 · $403,750

## Abstract

PROJECT SUMMARY
We discovered that innate immune activation facilitates nuclear reprogramming to pluripotency or to a different
cell lineage. Our characterization of this process (Lee et al, Cell 2012) 1 has produced new insights into the
mechanisms of nuclear reprogramming. We discovered that innate immune activation causes global changes
in the expression of epigenetic modifiers, associated with histone markings that favor nuclear reprogramming.
We intend to further elucidate the mechanisms by which innate immune activation facilitates direct
reprogramming (transdifferentiation). A major factor involved in innate immune response is the inducible
enzyme nitric oxide synthase (iNOS). Our data indicates that iNOS translocates to the nucleus during
transdifferentiation and may directly bind and S-nitrosylate epigenetic modifiers. Accordingly, we intend to:
1. Assess the direct effects of S-nitrosylation on epigenetic regulators during transdifferentiation. We will
assess the effect of S-nitrosylation on the activity of selected epigenetic factors, and/or their binding to co-
factors or chromatin, using immunoblot analyses, IP and ChIP, and the effect of genetic or pharmacologic
manipulation of iNOS. We will also elucidate the importance of iNOS translocation and its physical association
with epigenetic modifiers in transdifferentiation using genetic and pharmacological methods to disrupt iNOS
translocation and binding to selected epigenetic modifiers.
2. Characterize the effects of S-nitrosylation on DNA accessibility and fidelity of transdifferentiation.
We will characterize open chromatin regions using DNAse-Seq and Mnase-Seq; bivalent chromatin markings
by ChIP-seq, integrated with a global assessment of the transcriptional regulation (RNA-Seq) and determine
the importance of iNOS in the fidelity of epigenetic changes required for activation of cell identity genes.

## Key facts

- **NIH application ID:** 9906255
- **Project number:** 5R01HL133254-03
- **Recipient organization:** METHODIST HOSPITAL RESEARCH INSTITUTE
- **Principal Investigator:** JOHN P COOKE
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $403,750
- **Award type:** 5
- **Project period:** 2018-04-01 → 2022-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9906255

## Citation

> US National Institutes of Health, RePORTER application 9906255, Role of S-nitrosylation in Transdifferentiation (5R01HL133254-03). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9906255. Licensed CC0.

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