# SINGLE-CELL CHEMICAL TRANSCRIPTOMIC DISSECTION OF AN ESSENTIAL TRANSCRIPTION FACTOR NETWORK

> **NIH NIH DP2** · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · 2021 · $1

## Abstract

SINGLE-CELL CHEMICAL TRANSCRIPTOMIC DISSECTION OF AN ESSENTIAL TRANSCRIPTION
FACTOR NETWORK
PROJECT SUMMARY / ABSTRACT
Basic helix-loop-helix leucine zipper transcription factors (TFs) in the extended MYC network play essential roles
regulating cellular growth, differentiation, and homeostasis. Seminal studies have implicated MYC and its
interacting network of TFs as drivers of proliferation and metabolism in development and cancer, but how dosage
of these factors encodes transcriptional state remains contentious. Here, I propose a novel chemical genomic
framework to systematically determine how TF dosage, transcriptional output, and cellular state are linked. I will
combine our recently published massively multiplex single-cell RNA-seq screening method (sci-Plex) with
chemical genetic degradation of protein targets to examine how embryonic stem cells are transcriptionally
reprogrammed following dosed degradation of TFs. I will then employ state-of-the-art computational tools to
quantify the cellular state trajectories encoded by specific dosages. Finally, I will leverage this single-cell
‘perturbation atlas’ to support genomic mapping experiments to understand how reduced dosage of these factors
in vivo leads to physical redistribution across the genome. These studies will i.) illuminate mechanisms by which
TF dosages encode transcriptional output, ii.) elucidate how intracellular concentrations of interacting TFs
maintain chromatin, transcriptional, and cellular states, and iii.) provide mechanistic insight into how a
transcription factor network interacts with the epigenome to regulate mammalian pluripotency. More generally,
these approaches have the potential to address long-standing gene regulatory questions of how protein dosage
controls cellular state in both health and in cancer.

## Key facts

- **NIH application ID:** 10244771
- **Project number:** 1DP2HG012442-01
- **Recipient organization:** UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
- **Principal Investigator:** Vijay Ramani
- **Activity code:** DP2 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $1
- **Award type:** 1
- **Project period:** 2021-09-10 → 2021-11-03

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10244771

## Citation

> US National Institutes of Health, RePORTER application 10244771, SINGLE-CELL CHEMICAL TRANSCRIPTOMIC DISSECTION OF AN ESSENTIAL TRANSCRIPTION FACTOR NETWORK (1DP2HG012442-01). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10244771. Licensed CC0.

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