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Exploring Sequence Space to Identify Binding Sites for Regulatory RNA-Binding Proteins
Published on: August 9, 2019
Integrated genome analysis suggests that most conserved non-coding sequences are regulatory factor binding sites.
Martin Hemberg1, Jesse M Gray, Nicole Cloonan
1Department of Ophthalmology, Children's Hospital Boston, Harvard Medical School, Boston, MA 02215, USA. martin.hemberg@childrens.harvard.edu
Nucleic Acids Research
|June 12, 2012
Summary
Most conserved non-coding DNA in vertebrate genomes acts as regulatory elements, not non-coding RNAs. These elements, identified as regulatory factor binding sites (RFBSs), are crucial for gene regulation.
Area of Science:
- Genomics
- Molecular Biology
- Bioinformatics
Background:
- Vertebrate genomes contain vast non-coding DNA regions with unknown functions.
- Short, conserved sequences within non-coding DNA may encode non-coding RNAs (ncRNAs) or act as regulatory factor binding sites (RFBSs).
Purpose of the Study:
- To investigate the function of unannotated conserved islands in vertebrate genomes.
- To determine if these islands primarily encode ncRNAs or function as RFBSs, such as enhancers.
Main Methods:
- Compared unannotated conserved islands in human and mouse genomes to transcribed regions and RFBSs.
- Utilized RNA-Seq, ChIP-Seq, and DNAse-hypersensitivity assays to define transcribed regions and RFBSs.
- Applied a novel transcript-calling algorithm for RNA-Seq data analysis.
Main Results:
- Unannotated conserved islands are four times more likely to be RFBSs than ncRNAs.
- Identified thousands of conserved RFBSs as insulators (CTCF) or enhancers (p300/CBP, H3K4me1).
- Transcripts from these RFBSs are typically unspliced, non-polyadenylated, and expressed at low levels.
Conclusions:
- The majority of conserved non-coding DNA in vertebrate genomes functions as promoter-distal regulatory elements.
- These findings highlight the regulatory role of conserved non-coding sequences beyond protein-coding genes.
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