# Function of Putative Determinant in Hematopoiesis

> **NIH NIH R01** · ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI · 2020 · $650,688

## 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.
 Analysis of EKLF's ability to positively regulate transcription and chromatin has led to
identification of its association with the HIRA chaperone, and of its direct activation of histone H3.3
expression. The experiments of Aim 1 will link a coherent feed-forward model of the
EKLF/HIRA/H3.3 axis with changes in paused/active status at selected EKLF target genes.
 Analysis of expression patterns resulting from the neonatal anemia (Nan) mutation in murine
EKLF (E339D) shows extensive genetic disruption and exacerbated anemia that follows extensive
ectopic gene expression following Nan-EKLF expression. The experiments of Aim 2 will have
identified alterations in protein/protein interactions, mapped the changes in binding at normal
and novel target sites, and analyzed the resultant epigenetic rearrangements that follow from
Nan-EKLF expression.
 Analysis of DNA from a congenital dyserythropoietic anemia (CDA) patient supports the idea
that a subset (type IV) follows from mutation in one allele of human KLF1 at E325K. The experiments
of Aim 3 will have characterized derived iPSCs and de novo mutated erythroid cells for their
hematopoietic/erythroid cellular and expression capabilities as well as to enable molecular/
biochemical studies of the KLF1/E325K protein itself.
 These studies will be aided by the use of phenotypic and biochemical analyses, genetic
approaches, and use of primary or minimally manipulated cells. 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 and epigenetics.

## Key facts

- **NIH application ID:** 9897502
- **Project number:** 5R01DK046865-27
- **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:** 2020
- **Award amount:** $650,688
- **Award type:** 5
- **Project period:** 1993-08-01 → 2021-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9897502

## Citation

> US National Institutes of Health, RePORTER application 9897502, Function of Putative Determinant in Hematopoiesis (5R01DK046865-27). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9897502. Licensed CC0.

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