# Nuclear organization and its role in gene regulation

> **NIH NIH R35** · NEW YORK UNIVERSITY SCHOOL OF MEDICINE · 2024 · $742,410

## Abstract

SUMMARY:
My lab’s work has been at the forefront of studies showing that nuclear organization and long-range chromatin
interactions play an essential role in recombination and gene regulation. We combine molecular and imaging
(DNA/RNA FISH) approaches with in house generated computational pipelines, and are thus one of a handful
of labs that has expertise in both the experimental and analytical aspects of chromosome folding. In this
application we will extend our work to focus on two main interlinked problems of significant biological
importance: Project 1: Understanding bookmarking in the context of mitotic chromatin folding. In
mitosis (M), the promoters of M-phase active genes are “bookmarked” maintaining the accessibility of some
regulatory elements. This provides a mechanism for the rapid activation of a subset of genes, allowing cells
exiting from mitosis to preserve a memory of the epigenetic program of the previous cell cycle. Since
regulatory factors associate with chromatin with distinct affinities, some factors will be retained on M-phase
chromatin better than others, and furthermore, because binding occurs in a dynamic manner, sites at which
factors remain bound will not be uniform across a population of cells. The inefficiency of bookmarking,
combined with cell-to-cell variability, imparts daughter cells with a degree of epigenetic plasticity, enabling
them to alter their phenotype in response to environmental signals, which can have a significant impact on
developmental and biological processes. However, little is known about the mechanisms underlying this
process, and in particular how condensin II-mediated chromatin folding during mitosis impacts accessibility.
Project 2: Mechanisms underlying the chromatin organization and gene regulation of quiescent cells.
Cells can adapt and survive under conditions of stress, toxicity, nutrient or growth factor depletion/and
chemical insult, by exiting the cell cycle and entering a reversible dormant state known as quiescence (G0).
Previous studies showed that CTCF/cohesin-mediated TAD structure is restored after entry into G1, but
chromosome structure in mammalian G0 cells has not been studied carefully using modern molecular
methodologies. Gene expression is globally repressed in G0 cells, but we now know that quiescent cells
actively transcribe specific genes. Notably, chromatin in quiescent cells is predominantly compact, as in M
phase. Accordingly, we hypothesize that cells exiting M into G0 partially preserve the compact organization of
mitotic cells by retaining condensin II-mediated loops. The goal of our future studies is to determine whether
(i) condensin II binding at the start of M-phase functions to bookmark a subset of active promoters, (ii) whether
there is variability in the sites that are bookmarked between individual cells, and (iii) whether condensin II-
mediated chromatin looping and bookmarking are mechanistically linked to the unique genome organization
and transcription...

## Key facts

- **NIH application ID:** 10794320
- **Project number:** 5R35GM122515-08
- **Recipient organization:** NEW YORK UNIVERSITY SCHOOL OF MEDICINE
- **Principal Investigator:** Jane Amanda Skok
- **Activity code:** R35 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $742,410
- **Award type:** 5
- **Project period:** 2017-04-03 → 2027-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10794320

## Citation

> US National Institutes of Health, RePORTER application 10794320, Nuclear organization and its role in gene regulation (5R35GM122515-08). Retrieved via AI Analytics 2026-05-29 from https://api.ai-analytics.org/grant/nih/10794320. Licensed CC0.

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