# Regulatory Mechanisms of CD4+ T Cell Differentiation

> **NIH NIH UM1** · DUKE UNIVERSITY · 2021 · $984,751

## Abstract

Our ENCODE proposal aims to functionally characterize changes in gene regulation during the
differentiation of mouse CD4+ T cells. We have already accomplished major primary goals of identifying
regulatory elements that change activity during cell differentiation, and identifying regulatory elements
that are sufficient to drive cell differentiation. We also have ongoing Year 4 studies to achieve our Aim of
measuring effects of above-described regulatory elements on changes in gene expression during cell
differentiation. Finally, we have completed several cross-ENCODE coordinated studies of human K562
and WTC-11 cells as part of the coordinated functional characterization center effort, and are now
contributing to the comparative analysis of those results. We have five objectives of this request for an
extension of funding. First, we plan to make highly efficient use of the experimental systems we have
established to date to characterize gene targets of regulatory elements involved in CD4 T cell
differentiation. Second, we will continue our teams leadership in comparing results from different
functional characterization assays across the ENCODE consortium. Third, we will expand coordinated
functional characterization efforts to include study of the genomic response to glucocorticoids.
Glucocorticoid responses have been studied by ENCODE since 2008, and including functional
characterization studies of the system at the conclusion of ENCODE will create new synergies with
those previous data production efforts. We also view the theme of studying differential regulatory
element activity as particularly important because the elements identified and the methods used are
distinct from steady-state studies; and thus comparative analyses of how functional characterization
technologies perform when assaying differential regulatory effects will be invaluable for guiding the
future environmental response and perturbation studies. Fourth, we commit to submitting all data
generated to the ENCODE DCC. Fifth, we also commit to distributing all reagents, protocols and results
from comparative analyses for community use. The expected outcome of this extension of funding will
be to substantially enhance the utility of ENCODE to inform future genomics research, particularly that
involving high-throughput functional characterization assays and/or that involving environmental
responses. That outcome aligns with recommendations by the ECP to enhance ENCODE studies of
environmental response systems and to enhance coordination between data production and functional
characterization centers. Those outcomes will be particularly impactful in the legacy of ENCODE as the
NHGRI moves broadly to increase emphasis on studies of environmental responses and genomic
perturbations as part of the 2020 Strategic Plan.

## Key facts

- **NIH application ID:** 10240966
- **Project number:** 3UM1HG009428-04S1
- **Recipient organization:** DUKE UNIVERSITY
- **Principal Investigator:** GREGORY E CRAWFORD
- **Activity code:** UM1 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $984,751
- **Award type:** 3
- **Project period:** 2021-08-30 → 2022-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10240966

## Citation

> US National Institutes of Health, RePORTER application 10240966, Regulatory Mechanisms of CD4+ T Cell Differentiation (3UM1HG009428-04S1). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10240966. Licensed CC0.

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