Related Experiment Video
Updated: Aug 14, 2026
11:36
An Integrated Workflow to Study the Promoter-Centric Spatio-Temporal Genome Architecture in Scarce Cell Populations
Published on: April 21, 2023
Molecular co-accessibility identifies coordinated regulation between distant cis-regulatory elements
Mathias Boulanger1, Kasit Chatsirisupachai1, Yuliya Badayeva2
1European Molecular Biology Laboratory, Meyerhofstraße 1, 69117 Heidelberg, Germany.
Molecular Cell
|August 12, 2026
Summary
Gene expression relies on coordinated enhancer activation across DNA. This study reveals how cis-regulatory elements form networks, sharing accessibility to regulate transcription in fruit flies.
Area of Science:
- Genomics
- Molecular Biology
- Developmental Biology
Background:
- Gene expression in metazoans is controlled by cis-regulatory landscapes (CRLs) including promoters and enhancers.
- The coordination mechanisms of cis-regulatory elements (CREs) across large genomic distances are not fully understood.
- It remains unclear if simultaneous enhancer activation is necessary for transcription.
Purpose of the Study:
- To investigate the coordination of CRE function across entire CRLs in the Drosophila genome.
- To quantify the co-occurrence of chromatin accessibility and transcription factor binding across CRLs.
- To determine if coordinated enhancer activation is a widespread mechanism for gene regulation.
Main Methods:
- Combined single-molecule footprinting with long-read sequencing.
- Analyzed thousands of individual DNA molecules per locus in the Drosophila genome.
- Quantified chromatin accessibility and transcription factor binding across CRLs.
Main Results:
- CREs form specific networks with shared single-molecule chromatin accessibility profiles.
- Co-accessibility occurs between non-adjacent CREs, often facilitated by chromatin looping.
- Co-accessible CREs show coordinated cell-type-specific accessibility, linking enhancer activity to transcription.
Conclusions:
- Coordinated enhancer activation is a widespread mechanism regulating gene expression.
- Dependencies between CREs are observed genome-wide.
- This study provides insights into the functional networks of CREs in regulating transcription.
Related Concept Videos
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...
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...
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...
02:04Co-activators and Co-repressors
Gene transcription is regulated by the synergistic action of several proteins that form a complex at a gene regulatory site. This is observed in eukaryotes, where the regulation of gene expression is a complex process. Regulatory proteins in eukaryotes can broadly be classified into two types – regulators that bind directly to specific DNA sequences and co-regulators that associate with regulatory proteins but cannot directly bind to the DNA. These co-regulators are further divided into...
02:04Co-activators and Co-repressors
Gene transcription is regulated by the synergistic action of several proteins that form a complex at a gene regulatory site. This is observed in eukaryotes, where the regulation of gene expression is a complex process. Regulatory proteins in eukaryotes can broadly be classified into two types – regulators that bind directly to specific DNA sequences and co-regulators that associate with regulatory proteins but cannot directly bind to the DNA. These co-regulators are further divided into...