# Oscillatory gene expression and the maintenance of temporal patterning

> **NIH NIH R01** · COLD SPRING HARBOR LABORATORY · 2022 · $231,950

## Abstract

Project Abstract:
Developmental gene regulation is a multidimensional problem where signals converge to generate patterns of
transcription at the proper location (spatial regulation) and correct time (temporal regulation). An equally
important feature of this regulatory process involves generating the correct amount of transcription during
development as many key regulatory genes function in dosage sensitive manners where too much or too little
expression can lead to developmental defects or disease. At present, we have only a primitive understanding
about how the transcriptional output of developmentally regulated genes is established. Experiments outlined in
this proposal aim to directly address this problem by employing an in vivo imaging system in C. elegans larva
where GFP molecules are directly tethered to nascent RNAs while they are being actively transcribed in the
nucleus. This new platform enables us to directly quantify and model the real-time expression dynamics that
ultimately dictate transcriptional output of individual genes throughout development. In Aim 1, we will use this
system to dissect the mechanisms by which two transcription factors, BLMP-1 and LIN-42, modulate features of
transcriptional bursting (including burst frequency, duration, and amplitude) to tune transcriptional levels of key
microRNAs (including lin-4 and let-7) that dictate sequential patterns of cell fate specification. We will then probe
the genomic and molecular mechanisms that BLMP-1 employs to prime future transcription by remodeling
chromatin accessibility near target gene loci. In the final Aim, we will characterize the physical and functional
interactions between LIN-42 and several conserved nuclear hormone receptors (NHR-23RORg and NHR-85Rev-
erbb) that mediate temporal aspects of lin-4 and let-7 transcriptional activation. This avenue of research will reveal
the principles by which chromatin remodeling and its impact on modulating the transcriptional output of cyclically
expressed genes ensures the precision and robustness of cell fate specification during development.

## Key facts

- **NIH application ID:** 10653546
- **Project number:** 3R01GM117406-06A1S1
- **Recipient organization:** COLD SPRING HARBOR LABORATORY
- **Principal Investigator:** CHRISTOPHER Martin HAMMELL
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $231,950
- **Award type:** 3
- **Project period:** 2016-03-01 → 2026-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10653546

## Citation

> US National Institutes of Health, RePORTER application 10653546, Oscillatory gene expression and the maintenance of temporal patterning (3R01GM117406-06A1S1). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10653546. Licensed CC0.

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