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Updated: May 21, 2026
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High-throughput Identification of Gene Regulatory Sequences Using Next-generation Sequencing of Circular Chromosome Conformation Capture (4C-seq)
Published on: October 5, 2018
Comparative epigenomic annotation of regulatory DNA
Shu Xiao1, Dan Xie, Xiaoyi Cao
1Department of Bioengineering, University of Illinois at Urbana-Champaign, IL 61801, USA.
Cell
|June 12, 2012
Summary
Comparative epigenomics compares DNA and histone modifications across species to identify regulatory genome elements. This approach reveals conserved regulatory features not found through sequence analysis alone.
Area of Science:
- Genomics
- Epigenetics
- Evolutionary Biology
Background:
- Functional annotation of regulatory DNA sequences is challenging despite vast genomic data.
- Understanding regulatory elements is crucial for deciphering gene expression and cellular function.
Purpose of the Study:
- To introduce and validate comparative epigenomics as a method for annotating the regulatory genome.
- To identify conserved epigenomic patterns across species for regulatory element discovery.
Main Methods:
- Comparative epigenomics involving interspecies comparison of DNA and histone modifications.
- Genomic distribution analysis of cytosine methylation, histone marks (H2A.Z, H3K4me1/2/3, H3K9me3, H3K27me3, H3K27ac, H3K36me3), RNA, and transcription factor binding in human, mouse, and pig stem cells.
- Correlation analysis between epigenomic and transcriptomic evolutionary changes.
Main Results:
- Epigenomic conservation was observed in rapidly and slowly evolving DNA sequences, but not in neutrally evolving ones.
- A linear correlation was found between evolutionary changes in the epigenome and the transcriptome.
- Conserved colocalization of epigenomic marks successfully identified regulatory sequences, with seven pairs showing regulatory functions during embryonic stem cell differentiation.
Conclusions:
- Comparative epigenomics is a powerful approach for discovering regulatory genome features.
- Conserved epigenomic patterns provide insights into genome regulation beyond sequence comparisons.
- This method enhances the functional annotation of regulatory DNA sequences.
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01:37Epigenetic Regulation
Epigenetic changes alter the physical structure of the DNA without changing the genetic sequence and often regulate whether genes are turned on or off. This regulation ensures that each cell produces only proteins necessary for its function. For example, proteins that promote bone growth are not produced in muscle cells. Epigenetic mechanisms play an essential role in healthy development. Conversely, precisely regulated epigenetic mechanisms are disrupted in diseases like cancer.
X-chromosome...
X-chromosome...
01:46Epigenetic Regulation
Epigenetic mechanisms play an essential role in healthy development. Conversely, precisely regulated epigenetic mechanisms are disrupted in diseases like cancer.
01:46Epigenetic Regulation
Epigenetic mechanisms play an essential role in healthy development. Conversely, precisely regulated epigenetic mechanisms are disrupted in diseases like cancer.
02:02Cis-regulatory Sequences
Cis-regulatory sequences are short fragments of non-coding DNA that are present on the same chromosomes as the genes that they regulate. These fragments serve as binding sites for transcriptional regulators, proteins that are responsible for controlling gene transcription and differential gene expression across cell types in eukaryotes. Cis-regulatory sequences can be close to the gene of interest or thousands of bases away in the DNA sequence; however, those sequences that are further away are...
02:02Cis-regulatory Sequences
Cis-regulatory sequences are short fragments of non-coding DNA that are present on the same chromosomes as the genes that they regulate. These fragments serve as binding sites for transcriptional regulators, proteins that are responsible for controlling gene transcription and differential gene expression across cell types in eukaryotes. Cis-regulatory sequences can be close to the gene of interest or thousands of bases away in the DNA sequence; however, those sequences that are further away are...
02:13Cooperative Binding of Transcription Regulators
Transcriptional regulators bind to specific cis-regulatory sequences in the DNA to regulate gene transcription. These cis-regulatory sequences are very short, usually less than ten nucleotide pairs in length. The short length means that there is a high probability of the exact same sequence randomly occurring throughout the genome. Since regulators can also bind to groups of similar sequences, this further increases the chances of random binding. Transcriptional regulators form dimers that...