# Function of Putative Determinant in Hematopoiesis

> **NIH NIH R01** · ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI · 2022 · $642,939

## Abstract

SUMMARY
 Cell-restricted transcriptional modulators play critical roles in the process of selective gene
regulation during hematopoiesis. We have been investigating the molecular and biological function of
Erythroid Krüppel-like Factor (EKLF; KLF1). EKLF is a cell-restricted transcription factor that is a global
regulator of genes essential for the erythroid program. Our proposal builds on unanticipated novel
observations made during the previous funding cycle that extend this long-term study towards innovative
directions:
 We found that EKLF is modified at arginine residues by mono- and di-methylation. The
experiments of Aim 1 will address the context for these alterations and their function, and identify
the enzymes responsible.
 We found that the metabolomes of the mouse Nan-EKLF and human CDA-KLF1 mutant erythroid
cells are altered; this includes a metabolite involved in chromatin-associated changes in histone
modification. The experiments of Aim 2 will examine the global nature of these modifications in
mouse primary cells and in our newly-developed CDA patient-derived cell lines.
 We find that chromatin accessibility is altered in EKLF KO and in the Nan/+ cell. The
experiments of Aim 3 will examine these changes in the context of the sets of decreased and
ectopically expressed genes in these genetic backgrounds, an analysis that will be expanded to
include CDA patient-derived cells.
 We found that the metabolome of the EKLF KO cell is altered, and leads to changes in DNA
epigenetics. The experiments of Aim 4 will globally analyze these changes in the context of the
altered RNA expression and chromatin accessibility observed in the absence of EKLF.
 These studies will be aided by the use of molecular, metabolic, and biochemical analyses,
genetic approaches, and use of primary or minimally manipulated cells that have been newly
established. Elucidating EKLF’s role in regulatory phenomena will continue to illuminate novel aspects of
erythroid biology and the essential mechanisms by which a cell-restricted transcription factor can exert
varied yet highly controlled influences on genetic expression, metabolism, and epigenetics.

## Key facts

- **NIH application ID:** 10456190
- **Project number:** 5R01DK046865-29
- **Recipient organization:** ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI
- **Principal Investigator:** JAMES J BIEKER
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $642,939
- **Award type:** 5
- **Project period:** 1993-08-01 → 2025-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10456190

## Citation

> US National Institutes of Health, RePORTER application 10456190, Function of Putative Determinant in Hematopoiesis (5R01DK046865-29). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10456190. Licensed CC0.

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