# Interrogating YY1's role in chromatin organization during erythroid cell state transitions

> **NIH NIH F30** · UNIVERSITY OF PENNSYLVANIA · 2022 · $33,475

## Abstract

Project Summary
Chromatin structure plays an important role in instructing gene expression and maintaining cellular identity.
However, much remains unknown regarding how the genome becomes reorganized during crucial transitions,
such as cell cycle progression and cellular differentiation.
 Mitosis is marked by a global cessation of transcription, eviction of transcription factors, and the
dissolution of most chromatin structure. During the mitosis to G1 phase transition, newly born cells must
therefore address the challenge of rapidly re-establishing 3D genome organization that faithfully reflects that of
the mother cell. While CTCF and cohesin-mediated loop extrusion has been shown to forge some chromatin
loops, many observed architectural features cannot be explained by this mechanism. Another important
architectural factor, YY1, has been implicated in enhancer-promoter loops in studies in interphase cells.
However, its dynamics and role in chromatin loop formation has not been explored at the critical juncture
between mitosis and G1 phase. We aim to characterize YY1 chromatin occupancy kinetics as it relates to the
emergence of chromatin loops. We will test its necessity by interrogating effects of specifically timed depletion
during metaphase and during G1 phase entry. We also propose to study the functional importance of YY1-
mediated loop formation by characterizing transcriptional changes caused by mitotic depletion.
 Similarly, the role of YY1 in chromatin organization during hematopoiesis has yet to be clearly defined.
YY1 has been proposed to be a regulator of loops essential for development, but previous work has only
focused on select loci in limited cell types. To elucidate YY1’s involvement in genome reorganization during
developmental transitions, we will characterize YY1 binding and corresponding architectural changes by
generating high-resolution Micro-C maps before and after erythroblast maturation. We will also acutely deplete
YY1 during differentiation to test its necessity in orchestrating looping reconfiguration in erythroblasts.
 By utilizing two natural state transitions – cell cycle and erythroid differentiation – as well as an acute
degradation system, we aim to gain new insights into the fundamental mechanisms underlying genome
organization.

## Key facts

- **NIH application ID:** 10464524
- **Project number:** 1F30DK132824-01
- **Recipient organization:** UNIVERSITY OF PENNSYLVANIA
- **Principal Investigator:** Jessica Lam
- **Activity code:** F30 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $33,475
- **Award type:** 1
- **Project period:** 2022-07-01 → 2023-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10464524

## Citation

> US National Institutes of Health, RePORTER application 10464524, Interrogating YY1's role in chromatin organization during erythroid cell state transitions (1F30DK132824-01). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10464524. Licensed CC0.

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