# Investigating the role of Ldb1 in chromatin architecture and transcription during erythroid cell state transitions

> **NIH NIH F31** · UNIVERSITY OF PENNSYLVANIA · 2024 · $46,944

## Abstract

Project Summary
Chromatin architecture plays important regulatory roles in gene expression and is critical to maintain cellular
identity. However, there are many unanswered questions regarding the interplay between chromatin
architecture and transcriptional gene regulation, specifically regarding how one influences the other and what
factors are involved in orchestrating long-range regulatory chromatin contacts. My proposal attempts to
address these questions by focusing on an understudied architectural factor called Ldb1.
 Ldb1 has been studied at select loci and can facilitate long-range chromatin interactions between
regulatory elements and target genes. The direct role of Ldb1 in facilitating chromatin architecture genome-
wide to drive lineage-specific gene expression profiles during hematopoiesis has not been clearly defined. We
will characterize Ldb1’s role in these processes using a well-studied cellular model system for erythroid
differentiation. We will measure genome-wide features of chromatin architecture and Ldb1 genomic occupancy
during the dynamic process of erythroid maturation. Additionally, we will acutely deplete Ldb1 to test how and
to what extent it is required to maintain chromatin architectural features and gene expression profiles before
and after terminal erythroid differentiation.
 Additionally, we will exploit the natural and highly dynamic processes that occur during cell cycle
progression to test Ldb1’s role in establishing chromatin architectural features genome-wide. Mitosis is marked
by the eviction of transcription factors, dissolution of most chromatin structure and a global cessation of
transcription. During exit from mitosis, daughter cells must re-establish 3D chromatin architecture and
transcriptomes that reflect the cell identity of the mother cell. Many features of chromatin architecture arise
during mitotic exit through unknown mechanisms and are independent of well-studied architectural factors
such as CTCF and Cohesin. We will profile Ldb1 genomic occupancy at closely spaced timepoints during the
mitosis-G1 phase transition to determine if its binding dynamics are correlated with the formation of chromatin
structures. Furthermore, we will test the requirement of Ldb1 to establish features of chromatin architecture by
selectively depleting it in mitosis and measuring cell cycle progression and chromatin architecture reformation
genome-wide.
 By using two natural cell state transitions (erythroid differentiation and cell cycle progression) in addition
to acute degradation, we will glean new insights into the underlying mechanisms of chromatin architecture and
how they drive lineage-specific gene expression.

## Key facts

- **NIH application ID:** 10821758
- **Project number:** 1F31DK136200-01A1
- **Recipient organization:** UNIVERSITY OF PENNSYLVANIA
- **Principal Investigator:** Nicholas Aboreden
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $46,944
- **Award type:** 1
- **Project period:** 2024-09-01 → 2025-08-08

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10821758

## Citation

> US National Institutes of Health, RePORTER application 10821758, Investigating the role of Ldb1 in chromatin architecture and transcription during erythroid cell state transitions (1F31DK136200-01A1). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10821758. Licensed CC0.

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