# Structural Annotation of the Human Genome

> **NIH NIH R01** · UNIV OF MASSACHUSETTS MED SCH WORCESTER · 2024 · $731,774

## Abstract

PROJECT SUMMARY
 Cells must regulate their genome so that genes are expressed in the appropriate cell type, and at the
correct time. Further, as cells go through the cell cycle chromosomes must be replicated, compacted and then
faithfully segregated. All these processes require correct folding of the genome. Defects in folding, e.g., the
looping of genes to incorrect distal enhancers, or incorrect chromosome compaction during mitosis, can lead to
genes being expressed in the wrong place and at the wrong time, or to genome instability. Such defects can
lead to diseases including cancer. There has been tremendous progress in identifying folding principles of
chromosomes, how folding changes during the cell cycle, roles of cis elements in folding chromosomes and
long-range gene regulation, and the molecular machines and mechanisms that fold chromosomes. In
interphase chromosomes fold into topologically associating domains and cohesin-mediated loops.
Chromosomes also compartmentalize to form active and inactive chromatin domains through a phase
separation process. In mitosis, chromosomes refold into linearly compressed arrays of condensin-mediated
loops. We and others showed that alternation of cohesin-mediated loop formation and condensin-mediated
loop formation drives cell cycle stage-dependent chromosome folding. However, three critical aspects of
chromosome organization have remained largely unexplored, mostly due to lack of experimental approaches.
First, little is known about the identity of cis elements that mediate interactions between sister chromatids, yet
these interactions are critical for faithful chromosome segregation. Second, the topological state of
chromosomes, i.e., the presence of intra- and inter-chromosomal catenations is almost entirely unexplored.
Catenations form during replication and transcription and these create impediments to correct gene expression
and chromosome segregation and therefore the cell must constantly resolve these. Cis elements and trans
factors involved in controlling the topological state of the genome are largely uncharacterized. Third, factors
and cis elements driving chromosome compartmentalization are poorly characterized. We recently developed
three new genomic technologies, SisterC, Multi-Contact 3C, and Liquid Chromatin Hi-C that allow studying
each of these three outstanding questions respectively. Here, we will employ these methods to identify
genomic DNA elements, and their mode of action, that control chromosome compartmentalization, catenation
and decatenation, and that play roles in disentangling and segregating sister chromatids.

## Key facts

- **NIH application ID:** 10844390
- **Project number:** 5R01HG003143-19
- **Recipient organization:** UNIV OF MASSACHUSETTS MED SCH WORCESTER
- **Principal Investigator:** Job Dekker
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $731,774
- **Award type:** 5
- **Project period:** 2003-09-30 → 2027-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10844390

## Citation

> US National Institutes of Health, RePORTER application 10844390, Structural Annotation of the Human Genome (5R01HG003143-19). Retrieved via AI Analytics 2026-05-29 from https://api.ai-analytics.org/grant/nih/10844390. Licensed CC0.

---

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