# Chromatin Accessibility and Nuclear Localization Effects on Hematopoietic Lineage Fate

> **NIH NIH F31** · UNIVERSITY OF CALIFORNIA SANTA CRUZ · 2020 · $37,786

## Abstract

PROJECT SUMMARY:
Global chromatin reorganization and epigenetic changes govern the amazing ability of hematopoietic stem cells
to generate vastly different blood cell types. This control is achieved by gene level changes to chromatin
accessibility, controlled by the deposition of histone tail modifications that can either signal to condense a region
into heterochromatin, restricting access by transcription machinery and thereby “silencing” a gene; or by
performing the reciprocal function, relaxing the chromatin and making the DNA more accessible to transcription
machinery. Disruptions of these processes can cause gene dysregulation driving lineage commitment and
therefore cause disease. We seek to determine the underlying mechanisms during hematopoiesis that control
chromatin accessibility and gene localization that drive lineage commitment. The long-term goal of my project
is to determine the temporal dynamics of chromatin condensation and localization during blood cell
differentiation. Previous work in the lab has shown the ratio of heterochromatin to euchromatin increases as cells
differentiate from embryonic stems cells to hematopoietic stem cells to mature blood lineages. However, the
global levels of histone modifications did not change. In addition, H3K9me3, a known heterochromatin mark,
becomes localized towards the periphery of the nucleus during differentiation. These findings have led us to
hypothesize that normal blood differentiation requires silencing of pluripotency genes and alternative lineage
drivers by condensation into heterochromatin and sequestration to the nuclear lamina. We will test this
hypothesis by the following aims: Aim 1 will investigate how chromatin accessibility and nuclear localization
dynamics of genes throughout hematopoiesis affect lineage commitment, Aim 2 will determine the function of
chromatin localization to Lamin B1 and cis element accessibility during hematopoietic stem cell differentiation.
Completion of these aims will illuminate the epigenetic mechanisms that govern lineage fate decisions in
hematopoiesis. This knowledge can be leveraged to improve maintenance and expansion of HSCs in culture for
cell-replacement therapies and design strategies for preventing aberrant differentiation in hematopoietic
disorders and cancers.

## Key facts

- **NIH application ID:** 9961336
- **Project number:** 5F31HL144115-02
- **Recipient organization:** UNIVERSITY OF CALIFORNIA SANTA CRUZ
- **Principal Investigator:** Eric W Martin
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $37,786
- **Award type:** 5
- **Project period:** 2019-07-01 → 2021-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9961336

## Citation

> US National Institutes of Health, RePORTER application 9961336, Chromatin Accessibility and Nuclear Localization Effects on Hematopoietic Lineage Fate (5F31HL144115-02). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/9961336. Licensed CC0.

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