# Investigating the chromatin landscape of complex tissues through cell-type-specific patterns

> **NIH NIH F32** · FRED HUTCHINSON CANCER CENTER · 2024 · $73,828

## Abstract

Project Summary/Abstract
 The long-term objectives of this proposal include the following: 1) to generate cell-type-
specific chromatin profiles of the four cell types of the intestine, 2) to identify the effect crippled
silencing in intestinal stem cells has on progenitor cells, and 3) to characterize the
transcriptional changes associated with an age-related increase in the Polycomb Repressive
Complex-2 mark, H3K27me2, in the intestine. Cell-type-specific chromatin profiles aid the
specific gene expression patterns necessary for the function and identity of the cell. Complex
tissues are comprised of both stem and differentiated cells with different phenotypes,
transcriptional profiles, and roles within the tissue. The intestine contains a population of stem
cells responsible for replenishing damaged cells from the multiple stimuli exerted on the
intestine throughout the organism’s life span. However, the determining factors, especially at the
chromatin level, that make each cell type unique are unknown. Investigation into the chromatin
modifications of each cell type will provide insight into the unique roles each cell plays in the
function of the tissue. To generate gut cell-specific chromatin profiles, I will use CUT&Tag, a
robust and sensitive chromatin profiling technique that can be used with low cell numbers. I will
generate landscapes for chromatin modifications for all cell types of the gut to comprehensively
profile the epigenetic state of this tissue. Because of the importance of silencing modifications
for cellular identity and previous observations of loss of chromatin silencing affecting the gut
cells, I will investigate the effect of the loss of different chromatin silencing pathways in intestinal
stem cells on progenitor cells. Since the intestinal stem cells are the only mitotically active cells
in the intestine and the source of all other cells in the gut, their chromatin profiles likely affect the
progenitor cells. Additionally, observations of age-related increases in H3K27me2 in the
Drosophila melanogaster gut may indicate the protective role H3K27me2 has in preventing
pervasive transcription as tissue ages. The insights gained from this project will help us
understand the cell-type-specific chromatin profiles of cells of complex tissue and how
chromatin modification changes in stem cells affect their progenitors. My proposed project fits
the mission of NIGMS to fund research in fundamental biology that increases understanding of
the principles that underlie biological processes.

## Key facts

- **NIH application ID:** 10826745
- **Project number:** 1F32GM153148-01
- **Recipient organization:** FRED HUTCHINSON CANCER CENTER
- **Principal Investigator:** Sarah Leichter
- **Activity code:** F32 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $73,828
- **Award type:** 1
- **Project period:** 2024-01-01 → 2026-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10826745

## Citation

> US National Institutes of Health, RePORTER application 10826745, Investigating the chromatin landscape of complex tissues through cell-type-specific patterns (1F32GM153148-01). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10826745. Licensed CC0.

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