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Mapping the Structure-Function Relationships of Disordered Oncogenic Transcription Factors Using Transcriptomic Analysis

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Nucleome Analysis Reveals Structure-Function Relationships for Colon Cancer.

Laura Seaman¹, Haiming Chen¹, Markus Brown²

¹Department of Computational Medicine and Bioinformatics, University of Michigan, Ann Arbor, Michigan.

Molecular Cancer Research : MCR

|March 5, 2017

Summary

Chromosomal aberrations in cancer alter the relationship between nuclear structure and gene expression. New methods reveal how these changes impact chromatin accessibility and transcription in cancer cells.

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Associated Chromosome Trap for Identifying Long-range DNA Interactions

Associated Chromosome Trap for Identifying Long-range DNA Interactions

Published on: April 23, 2011

Area of Science:

Genomics and Molecular Biology
Cancer Research
Epigenetics and Nuclear Organization

Background:

Chromosomal translocations and aneuploidy are common in cancer genomes.
The impact of these genomic aberrations on the nucleome (nuclear structure and gene expression) remains poorly understood.

Purpose of the Study:

To analyze the nucleome of the colorectal cancer cell line HT-29.
To investigate the relationship between genome structure and gene expression in the context of chromosomal aberrations.
To develop novel methods for analyzing Hi-C data in cancer cells.

Main Methods:

Chromosome conformation capture (Hi-C) was used to study genome structure.
RNA sequencing (RNA-seq) was employed to assess genome function.
A new copy number-based normalization method for Hi-C data was developed.

Main Results:

High-resolution identification of translocations and copy number changes from Hi-C data.
Demonstration that structure-function relationships are maintained in cancer cells.
Increased correlation between chromatin organization and gene expression at translocation sites, indicating direct reflection of transcription by chromatin accessibility.
Identification of interactions between the MYC oncogene locus (8q24) and other genomic regions, characterized by open chromatin.

Conclusions:

Chromosome conformation capture can identify chromosomal abnormalities at high resolution in cancer.
Chromosomal aberrations alter the relationship between nuclear structure and gene expression.
The developed methods are applicable to assessing the nucleome in other cell types with chromosomal aberrations.