Annotation of Cis-Regulatory Elements by Identification, Subclassification, and Functional Assessment of Multispecies Conserved Sequences

An important step toward improving the annotation of the human genome is to identify cis-acting regulatory elements from primary DNA sequence. One approach is to compare sequences from multiple, divergent species. This approach distinguishes multispecies conserved sequences (MCS) in noncoding region...

Full description

Saved in:
Bibliographic Details
Published in:Proceedings of the National Academy of Sciences - PNAS 2005-07, Vol.102 (28), p.9830-9835
Main Authors: Hughes, Jim R., Cheng, Jan-Fang, Ventress, Nicki, Prabhakar, Shyam, Clark, Kevin, Anguita, Eduardo, De Gobbi, Marco, de Jong, Pieter, Rubin, Eddy, Higgs, Douglas R., Weatherall, David
Format: Article
Language:English
Subjects:
Animals
Base Sequence
Binding sites
Biological Sciences
Classification
Computational Biology - methods
Conserved Sequence - genetics
Conserved sequences
Deoxyribonucleic acid
DNA
Exons
GATA transcription factors
Gene Components - genetics
Genes
Genome, Human
Genomes
Genomics
Genomics - methods
Globins - genetics
Humans
Mammals
Molecular Sequence Data
Monkeys
Rats
Regulatory Sequences, Nucleic Acid - genetics
Sequence Alignment
Sequence Analysis, DNA
Species Specificity
Wildlife conservation
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:An important step toward improving the annotation of the human genome is to identify cis-acting regulatory elements from primary DNA sequence. One approach is to compare sequences from multiple, divergent species. This approach distinguishes multispecies conserved sequences (MCS) in noncoding regions from more rapidly evolving neutral DNA. Here, we have analyzed a region of ≈238kb containing the human α globin cluster that was sequenced and/or annotated across the syntenic region in 22 species spanning 500 million years of evolution. Using a variety of bioinformatic approaches and correlating the results with many aspects of chromosome structure and function in this region, we were able to identify and evaluate the importance of 24 individual MCSs. This approach sensitively and accurately identified previously characterized regulatory elements but also discovered unidentified promoters, exons, splicing, and transcriptional regulatory elements. Together, these studies demonstrate an integrated approach by which to identify, subclassify, and predict the potential importance of MCSs.
ISSN:0027-8424
1091-6490
DOI:10.1073/pnas.0503401102