# Underlying chromatin architecture defines functionality for CFTR expression

> **NIH NIH R01** · ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI · 2022 · $423,750

## Abstract

PROJECT SUMMARY:
The overall goal of this application is to elucidate the biological impact of chromatin remodeling for the
regulation of the cystic fibrosis transmembrane conductance regulator gene (CFTR) locus. In turn, a novel
understanding of chromatin remodeling processes linked with gene transcription may enable novel approaches
to targeted therapy for enriching weak (or poor) CFTR expression that appear consistent with specific
mutations in CFTR. This new knowledge coincides with the overall expectation to understand the complex
relationship of CFTR expression to cystic fibrosis (CF). CF remains a prominent genetic defect where
significant progress has been made in prenatal diagnosis and treatment. While many coding mutations in the
CFTR gene have been identified and casually linked to CF as a human disease, various non-genic
polymorphisms remain an unknown contributor the spectrum of disease outcomes link to the CFTR gene and
its expression. We, and others, have provided new insight about the chromatin architecture behind the CFTR
locus that gives rise to the selective epithelial cell-type and development control of CFTR transcription. In the
previous funding cycle we have identified and confirmed the role of the chromo-helicase DNA binding domain
protein 6 (CHD6) lies at the core of the topologically well-organized CFTR gene in native chromatin. This has
provided new insight as to the factors that govern how CFTR is arranged in the chromatin context in cultured
and primary cells. Together, through the aims proposed we expect to provide the fundamental framework to
determine how CFTR expression is guiding under a native chromatin context. We envision that these studies
will deepen our understanding of the means chromatin regulators use to shape the epithelial cell epigenome to
accommodate CFTR expression.

## Key facts

- **NIH application ID:** 10477362
- **Project number:** 5R01DK118946-05
- **Recipient organization:** ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI
- **Principal Investigator:** Martin John Walsh
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $423,750
- **Award type:** 5
- **Project period:** 2018-09-20 → 2024-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10477362

## Citation

> US National Institutes of Health, RePORTER application 10477362, Underlying chromatin architecture defines functionality for CFTR expression (5R01DK118946-05). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10477362. Licensed CC0.

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