Comparative genome analysis delimits a chromosomal domain and identifies key regulatory elements in the alpha globin cluster.
Hum Mol Genet
; 10(4): 371-82, 2001 Feb 15.
Article
em En
| MEDLINE
| ID: mdl-11157800
ABSTRACT
We have cloned, sequenced and annotated segments of DNA spanning the mouse, chicken and pufferfish alpha globin gene clusters and compared them with the corresponding region in man. This has defined a small segment ( approximately 135-155 kb) of synteny and conserved gene order, which may contain all of the elements required to fully regulate alpha globin gene expression from its natural chromosomal environment. Comparing human and mouse sequences using previously described methods failed to identify the known regulatory elements. However, refining these methods by ranking identity scores of non-coding sequences, we found conserved sequences including the previously characterized alpha globin major regulatory element. In chicken and pufferfish, regions that may correspond to this element were found by analysing the distribution of transcription factor binding sites. Regions identified in this way act as strong enhancer elements in expression assays. In addition to delimiting the alpha globin chromosomal domain, this study has enabled us to develop a more sensitive and accurate routine for identifying regulatory elements in the human genome.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Globinas
/
Sequências Reguladoras de Ácido Nucleico
/
Família Multigênica
/
Cromossomos
Tipo de estudo:
Prognostic_studies
Limite:
Animals
/
Humans
Idioma:
En
Revista:
Hum Mol Genet
Assunto da revista:
BIOLOGIA MOLECULAR
/
GENETICA MEDICA
Ano de publicação:
2001
Tipo de documento:
Article
País de afiliação:
Reino Unido