# Mapping the short-range chromatin architecture of the repressive epigenome

> **NIH NIH F32** · ROCKEFELLER UNIVERSITY · 2022 · $67,582

## Abstract

Project Summary
Genome architecture is associated with many essential cellular processes from transcriptional regulation to
chromosome segregation. Recent technological innovations have enabled detailed characterization of long-
range chromosome conformations. Long-range chromosome compaction appears at repressive regions
collectively referred to as heterochromatin. These genomic regions are vital for proper cell type-dependent
gene expression patterns, and their architecture also helps to protect against genomic instability by controlling
the expression of parasitic transposons and by regulating the chromatin structure near centromeres,
telomeres, and other DNA repeats. Despite advances in understanding long-range chromatin compaction, few
methods exist that measure the spatial organization of DNA at sub-nucleosome resolution, which is the length
scale relevant to transcription and other critical DNA processes. Furthermore, many heterochromatic structures
contain DNA repeats, which are difficult to study due to their inability to be mapped to a single genomic locus.
I seek to determine the short-range compaction states of heterochromatin, using a recently developed method,
RICC-seq, which can measure 3D DNA contacts at sub-nucleosome resolution. I will create new RICC-seq-
based methods using Nanopore long-read sequencing to enable measurements of DNA repeats. I will also
genetically manipulate histone modification pathways that regulate heterochromatin to determine their effects
on short-range chromatin structure. Histone deacetylation and methylation are two major epigenetic pathways
that dynamically regulate heterochromatin. In addition to these modifications, multiple isoforms of the
conserved heterochromatin protein 1 (HP1) help regulate heterochromatin structures. I will determine the
respective in vivo contributions that these epigenetic factors have on chromatin compaction and transcriptional
silencing. In addition to defining the basic rules governing heterochromatin organization and function, I also
propose to investigate the compaction states of phase-separated condensates. Phase separation is thought to
regulate heterochromatin dynamics and transcription, however, how it affects short-range chromatin
organization has yet to be addressed. I will determine the 3D DNA folding conformations of in vitro phase-
separated chromatin, connecting phenomena observed in vitro with measurements of chromatin compaction in
cells. This proposed work will tease out fundamental principles of genomic organization at nanoscale resolution
and provide a structural foundation for understanding heterochromatin regulation and the possible impacts of
its disruption in disease states.

## Key facts

- **NIH application ID:** 10319924
- **Project number:** 5F32GM140551-02
- **Recipient organization:** ROCKEFELLER UNIVERSITY
- **Principal Investigator:** Andres Mansisidor
- **Activity code:** F32 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $67,582
- **Award type:** 5
- **Project period:** 2021-01-01 → 2023-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10319924

## Citation

> US National Institutes of Health, RePORTER application 10319924, Mapping the short-range chromatin architecture of the repressive epigenome (5F32GM140551-02). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10319924. Licensed CC0.

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