# Tissue biology studies of histone modification, nascent transcription, and post-transcription regulation

> **NIH NIH R01** · CORNELL UNIVERSITY · 2024 · $553,544

## Abstract

Abstract
Basic cellular processes essential to mammalian tissue development and adult regeneration, are
often controlled by gene expression regulation at the mRNA level. Total mRNA level for each
gene depends on two mechanisms: active (or ‘nascent’) transcription and post-transcriptional
RNA stability/degradation (e.g. turnover rates). Nascent transcription itself is regulated by
multiple steps of recruiting histone-modifying enzymes and opening chromatin, RNA polymerase
II (Pol II) initiation and pausing, and the release of Pol II into productive RNA elongation. Diverse
mechanisms that regulate total mRNA level may be important in controlling distinct biological
processes and pathologies, but this is poorly understood in vivo. Using skin as a model system
we will map lineage-specific gene patterns of RNA Pol II activity and nascent transcription in
specific cell-types within their natural tissue milieu in the absence of cell isolation. Furthermore,
we will investigate changes in these nascent-transcription patterns along an adult tissue stem cell
activation and differentiation path, using hair follicle as a lineage prototype. In addition, our work
will help dissect relative contributions of active transcription vs post-transcriptional RNA
turnover/stability to overall mRNA levels in specific cell types in vivo. Furthermore, we will
determine how a known histone repressive mark (H3K9me3), poorly understood in mammalian
tissues, acts on nascent transcription and RNA Pol II pausing in vivo. We will uncover for the first
time the physiological role of the 3 main H3K9me3 histone methyl transferases in skin
development and homeostasis. Finally, we will investigate how H3K9me3 acts on nascent
transcription in vivo using our newly developed mouse genetics tools and methodologies. Our
work will provide previously unavailable mechanistic insight into gene regulation in mammalian
tissue biology using skin as a model system.

## Key facts

- **NIH application ID:** 10894126
- **Project number:** 5R01AR073806-07
- **Recipient organization:** CORNELL UNIVERSITY
- **Principal Investigator:** JOHN T LIS
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $553,544
- **Award type:** 5
- **Project period:** 2018-07-01 → 2028-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10894126

## Citation

> US National Institutes of Health, RePORTER application 10894126, Tissue biology studies of histone modification, nascent transcription, and post-transcription regulation (5R01AR073806-07). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10894126. Licensed CC0.

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