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Related Concept Videos

Cis-regulatory Sequences02:02

Cis-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...
Cis-regulatory Sequences02:02

Cis-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...
Multi-species Conserved Sequences02:51

Multi-species Conserved Sequences

Next-generation sequencing technologies have created large genomic databases of a variety of animals and plants. Ever since the human genome project was completed, scientists studied the genome of primates, mammals, and other phylogenetically distant living beings. Such large-scale  studies have provided new insights into the evolutionary relationship between organisms.
Although the genome of each species varies greatly from each other, a few sequences are highly conserved. Such conserved DNA...
Cooperative Binding of Transcription Regulators02:13

Cooperative 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...
Cooperative Binding of Transcription Regulators02:13

Cooperative 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...
Combinatorial Gene Control02:33

Combinatorial Gene Control

Combinatorial gene control is the synergistic action of several transcriptional factors to regulate the expression of a single gene. The absence of one or more of these factors may lead to a significant difference in the level of gene expression or repression.
The expression of more than 30,000 genes is controlled by approximately 2000-3000 transcription factors. This is possible because a single transcription factor can recognize more than one regulatory sequence. The specificity in gene...

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Related Experiment Video

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HOX Loci Focused CRISPR/sgRNA Library Screening Identifying Critical CTCF Boundaries
10:10

HOX Loci Focused CRISPR/sgRNA Library Screening Identifying Critical CTCF Boundaries

Published on: March 31, 2019

Multigenome DNA sequence conservation identifies Hox cis-regulatory elements.

Steven G Kuntz1, Erich M Schwarz, John A DeModena

  • 1Division of Biology, California Institute of Technology, Pasadena, California 91125, USA.

Genome Research
|November 5, 2008
PubMed
Summary
This summary is machine-generated.

Ungapped sequence comparisons effectively predict cis-regulatory elements in Caenorhabditis elegans. This method identified functional elements with high specificity and recovery rates, even across species.

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High-throughput Identification of Gene Regulatory Sequences Using Next-generation Sequencing of Circular Chromosome Conformation Capture (4C-seq)
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Mosaic Zebrafish Transgenesis for Evaluating Enhancer Sequences
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Area of Science:

  • Genomics
  • Developmental Biology
  • Bioinformatics

Background:

  • Identifying cis-regulatory elements (CREs) is crucial for understanding gene regulation.
  • Comparative genomics is a powerful tool for discovering conserved non-coding sequences, potential CREs.
  • The ceh-13/lin-39 locus in Caenorhabditis elegans provides a complex model for testing prediction methods.

Purpose of the Study:

  • To evaluate the efficacy of ungapped sequence comparisons for predicting CREs in C. elegans.
  • To assess how different genomes and comparison parameters influence prediction accuracy.
  • To identify functional CREs within the ceh-13/lin-39 locus using comparative genomics.

Main Methods:

  • Sequenced portions of C. brenneri and C. sp. 3 PS1010 genomes.
  • Compared five Caenorhabditis species genomes (C. elegans, C. briggsae, C. brenneri, C. remanei, C. sp. 3 PS1010).
  • Developed and applied the MUSSA program for N-way transitive conservation analysis on 22.8 kb of noncoding sequence.
  • Performed transgenic assays on 21 conserved regions.

Main Results:

  • Identified 10 functional CREs within the ceh-13/lin-39 locus with 100% specificity and 77% recovery rate.
  • One highly conserved element from a mouse Hox cluster recapitulated native nematode expression patterns in C. elegans.
  • Prediction quality varied with genome choice and comparison parameters.

Conclusions:

  • Ungapped sequence comparisons are a reliable method for predicting CREs genome-wide.
  • Comparative genomics, including cross-species comparisons, can successfully identify functional regulatory elements.
  • The MUSSA program and transgenic validation provide a robust framework for CRE discovery.