# Core A - Establishing the regulatory mechanisms defining cellular function

> **NIH NIH P01** · MASSACHUSETTS GENERAL HOSPITAL · 2024 · $491,490

## Abstract

Project Summary
The coordinated regulation of chromatin structure, transcription factor binding and RNA
expression is fundamental to cellular differentiation. Methods for measuring different layers of
gene regulation within single cells can be used to determine essential regulators of cell
differentiation and function as sensitive markers of cellular identity and lineage potential. To this
end, we (Buenrostro) have recently developed SHARE-seq (Simultaneous High-throughput
ATAC and RNA Expression with sequencing), for joint measurement of chromatin accessibility
and gene expression within the same single-cell, at low-cost and massive throughput. Using
SHARE-seq, we have shown that co-analysis of ATAC- and RNA-seq data from the same cell
can be used to associate transcription factors to their target regulatory regions and distal
regulatory elements to their target genes, enabling the definition of causal gene regulatory
networks. Furthermore, we have shown that changes in chromatin accessibility precedes changes
in gene expression, foreshadowing lineage commitment, and identifying a role for chromatin
accessibility in priming chromatin for gene activation. Here, we propose the establishment of the
Gene Regulation Core (GRC), which will be led by Dr. Jason Buenrostro at Harvard University's
Department of Stem Cell and Regenerative Biology. As part of this P01 proposal, the GRC will
enable the P01 members with SHARE-seq and other genomic technologies established in the
Buenrostro lab, which can be used to functionally annotate regulatory regions, identify key
transcription factors and chromatin regulators, define gene regulatory networks and parse cellular
states. The GRC will work closely with the P01 labs to design experiments, and organize and
collect hematopoietic samples (Aim 1). The GRC will use SHARE-seq to jointly profile chromatin
accessibility and RNA expression at the single cell level. This will include extending SHARE-seq
to capabilities uniquely enabled by SHARE-seq, such as the readout of transcribed lineage
barcodes and Clonal Hematopoiesis-associated mutations (Aim 2). Finally, the GRC will be
responsible for the primary processing of the data, data management, developing web interface
tools and organizing data discussions and workshops between the P01 labs (Aim 3). Overall, the
GRC will offer a complete solution for the single-cell genomics needs of the P01 community
through a unique and innovative suite of genomic technologies.

## Key facts

- **NIH application ID:** 10840850
- **Project number:** 5P01HL131477-07
- **Recipient organization:** MASSACHUSETTS GENERAL HOSPITAL
- **Principal Investigator:** Jason Daniel Buenrostro
- **Activity code:** P01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $491,490
- **Award type:** 5
- **Project period:** 2017-04-07 → 2028-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10840850

## Citation

> US National Institutes of Health, RePORTER application 10840850, Core A - Establishing the regulatory mechanisms defining cellular function (5P01HL131477-07). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10840850. Licensed CC0.

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