# Mechanisms of condensin-mediated gene regulation in C. elegans

> **NIH NIH R35** · NEW YORK UNIVERSITY · 2022 · $390,204

## Abstract

PROJECT SUMMARY/ABSTRACT
Regulation of chromosome structure is fundamental for genome function. Across eukaryotes, a key regulator of
chromosome structure is an evolutionarily conserved protein complex called condensin, which is essential for
chromosome condensation and segregation during cell division and play key roles in gene regulation during
interphase. The molecular mechanisms behind how condensins bind and regulate chromosome structure and
how this affects transcription remain unclear. To address this, we use a specialized condensin that functions
within the X chromosome dosage compensation complex (DCC) in C. elegans. DCC specifically binds to and
represses transcription of both X chromosomes in hermaphrodites by a factor of two. The co-option of
condensin for X chromosome dosage compensation provides a powerful experimental model to study the
mechanisms that control specificity of condensin binding and to analyze condensin-mediated changes in
chromosome structure and transcription with high precision, all free from potential indirect effects on
chromosome segregation.
Our previous work suggests that specific and robust DCC binding to the X chromosomes is accomplished by a
step-wise recruitment mechanism followed by linear spreading. First, DCC enters the chromosome at a small
number of X-specific sites defined by two genomic features: the presence of multiple 12-bp recruitment motifs
and overlap with high occupancy transcription factor target sites. After X-specific entry, additional sites
cooperate over long-distance to increase the level of DCC recruitment across the chromosome. From the
recruitment sites, DCC spreads linearly along large chromosomal domains, accumulating at active gene
regulatory elements across the X. DCC binding leads to chromosome-wide transcriptional repression, changes
in the level of specific histone modifications, chromosome compaction, and long-range chromosomal
interactions. Here, we will address several important questions regarding DCC recruitment, spreading and
function using a powerful set of genetic, genomic and imaging approaches: 1) How does the DCC recognize
features of the initial entry sites on the X? 2) What is the mechanism behind long-distance cooperation
between DCC recruitment elements? 3) How is DCC spreading and DCC-mediated chromosomal interactions
regulated? 4) What is the mechanism by which the DCC represses transcription?
The outcome of our work will elucidate the basic molecular mechanisms by which condensins perform their
wide-range of essential functions in eukaryotes. This is relevant to human health because condensin structure
and function is deeply conserved from C. elegans to humans, and determining how condensins function is key
to understanding the contribution of chromosome structure to genome function in health and disease.

## Key facts

- **NIH application ID:** 10410364
- **Project number:** 5R35GM130311-04
- **Recipient organization:** NEW YORK UNIVERSITY
- **Principal Investigator:** Sevinc Ercan
- **Activity code:** R35 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $390,204
- **Award type:** 5
- **Project period:** 2019-08-01 → 2024-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10410364

## Citation

> US National Institutes of Health, RePORTER application 10410364, Mechanisms of condensin-mediated gene regulation in C. elegans (5R35GM130311-04). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10410364. Licensed CC0.

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