# Transcriptional and Translational Regulation in Erythroid Cells

> **NIH NIH P01** · NEW YORK BLOOD CENTER · 2020 · $206,445

## Abstract

PROJECT SUMMARY/ABSTRACT
Transcriptional and Translational Regulation in Erythropoiesis
 Project 2 - Patrick G. Gallagher, PI
Erythrocytes are highly specialized cells that have evolved to efficiently carry out their primary functions of
oxygen transport and delivery. Unique patterns of gene regulation and expression direct a precise ensemble of
proteins required for erythrocyte structure and function. The overall goal of this proposal is to characterize and
integrate data from transcription, epigenetic, and translation-based studies in human erythroid cells of differing
developmental and differentiation stage to advance of our understanding of normal and perturbed
erythropoiesis. In specific aim one, chromatin architecture, DNA methylation status, and genomic organization
will be correlated with programs of gene expression at different stages of erythropoiesis. These studies will
address the hypothesis that varying epigenetic patterns determine programs of gene expression influencing
erythroid cell development and differentiation. Stage-specific enhancer repertoires will be identified and
enhancers correlated with genes associated with known erythroid cell traits and diseases. Correlative studies
will be performed in a TET2-deficient model of myelodysplastic syndrome (MDS), in uncultured primary
erythroid cells isolated from bone marrow of TET2-mutant MDS patients, and erythroid cells with altered lamin
A and lamin B1 levels across terminal erythroid differentiation. Control of gene expression at the level of
translation is now recognized to be as important as transcriptional regulation. In specific aim two, profiles of
proteins undergoing mRNA translation and their abundance will be characterized during erythropoiesis.
Defining and characterizing the abundance of proteins translated at differing stages of erythropoiesis will
provide novel insights into protein structure, function, and abundance throughout erythroid commitment,
development, and differentiation. These studies will address the hypothesis that varying patterns of mRNA
translation, determined by stage-specific regulatory programs, determine the programs of protein expression
that play critical roles in homeostatic cell growth and proliferation and specific patterns of dysregulated
translation are associated with inherited hematologic disease. Protein profiles obtained by ribosomal profiling
will be correlated with mRNA expression, epigenetic, and proteomics data sets. Correlative studies will be
performed to assess the influence of RPL5 or RPL11 deficiency on ribosomal profiles on a global, cellular
stage-specific scale in a model of Diamond Blackfan anemia. Integration of data from combinations of
transcription, epigenetic, translational and metabolic-based studies will allow hematology investigators to
create and compare high-resolution, global maps of relevant interactions driving gene expression and protein
production in erythroid cells of differing differentiation and developme...

## Key facts

- **NIH application ID:** 10013232
- **Project number:** 5P01DK032094-32
- **Recipient organization:** NEW YORK BLOOD CENTER
- **Principal Investigator:** PATRICK G GALLAGHER
- **Activity code:** P01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $206,445
- **Award type:** 5
- **Project period:** 1997-01-30 → 2022-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10013232

## Citation

> US National Institutes of Health, RePORTER application 10013232, Transcriptional and Translational Regulation in Erythroid Cells (5P01DK032094-32). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10013232. Licensed CC0.

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