# Structural Annotation of the Human Genome

> **NIH NIH R01** · UNIV OF MASSACHUSETTS MED SCH WORCESTER · 2021 · $748,392

## Abstract

Summary
The three-dimensional organization of the genome is critical for regulation of gene
expression, maintenance of genome stability and chromosome inheritance. Over the last
several years there has been a tremendous increase in our knowledge of the spatial
arrangements of chromosomes, and this is leading to insights into the molecular
mechanisms that regulate genes, and how defects in genome folding can lead to human
disease. We have developed powerful molecular and genomic technologies based on
chromosome conformation capture (3C, 5C, Hi-C) to probe the three-dimensional
structure of chromosomes. As cells go through the cell division cycle chromosomes
alternate between two entirely different spatial conformations. We and others have used
3C-based assays to determine the structure of the human genome in interphase and in
metaphase. In interphase the genome is composed of several different types of
chromosomal domains, while within these domains genes are regulated by specific
looping interactions between genes and their regulatory elements. A different structure is
observed in mitotic cells, when chromosomes become highly compacted. We discovered
that in mitosis chromosomes fold as linear arrays of consecutive chromatin loops. We
have delineated a series of folding intermediates that show how the interphase
conformation is converted into the metaphase state. These intermediates include
extended linear loop arrays in prophase and more compacted helical arrays of nested
loops in prometaphase. These studies lead to important new questions that we aim to
address. First, it is not known in genomic detail how during prophase the interphase
state is erased, chromosomes form initial loop arrays and sister chromatids become
separated. Second, very little is known about the molecular machines that fold
chromosomes. We propose innovative new strategies to identify new components of
these machines that act during mitosis and interphase. Third, we hypothesize that these
machines act through specific cis-elements that determine how and where they get
loaded onto chromosomes, move to new sites and accumulate at yet other sites. We will
identify and characterize these DNA elements that encode how the genome folds. Our
proposed studies will uncover how the genome folds, unfolds and refolds.

## Key facts

- **NIH application ID:** 10163890
- **Project number:** 5R01HG003143-17
- **Recipient organization:** UNIV OF MASSACHUSETTS MED SCH WORCESTER
- **Principal Investigator:** Job Dekker
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $748,392
- **Award type:** 5
- **Project period:** 2003-09-30 → 2023-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10163890

## Citation

> US National Institutes of Health, RePORTER application 10163890, Structural Annotation of the Human Genome (5R01HG003143-17). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10163890. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*