Cis-acting sequences regulating expression of the human alpha-globin cluster lie within constitutively open chromatin.
Current models suggest that tissue-specific genes are arranged in discrete, independently controlled segments of chromatin referred to as regulatory domains. Transition from a closed to open chromatin structure may be an important step in the regulation of gene expression. To determine whether the human alpha-globin cluster, like the beta-globin cluster, lies within a discrete, erythroid-specific domain, we have examined the long-range genomic organization and chromatin structure around this region. The alpha genes lie adjacent to at least four widely expressed genes. The major alpha-globin regulatory element lies 40 kb away from the cluster within an intron of one of these genes. Therefore, unlike the beta cluster, cis-acting sequences controlling alpha gene expression are dispersed within a region of chromatin that is open in both erythroid and nonerythroid cells. This implies a difference in the hierarchical control of alpha- and beta-globin expression.
Vyas
P
P
MRC Molecular Haematology Unit, Institute of Molecular Medicine, John Radcliffe Hospital, Oxford, England.
Vickers
M A
MA
Simmons
D L
DL
Ayyub
H
H
Craddock
C F
CF
Higgs
D R
DR
D000818:Animals; D015152:Blotting, Northern; D002460:Cell Line; D002843:Chromatin / Q000378:metabolism*; D003850:Deoxyribonuclease I / Q000378:metabolism; D005786:Gene Expression Regulation / Q000235:genetics*; D005914:Globins / Q000235:genetics*; D006801:Humans; D007438:Introns / Q000235:genetics; D008745:Methylation; D005810:Multigene Family / Q000235:genetics*; D012045:Regulatory Sequences, Nucleic Acid / Q000235:genetics*; D012091:Repetitive Sequences, Nucleic Acid / Q000235:genetics; D014407:Tumor Cells, Cultured
D002843:Chromatin; D005914:Globins; D003850:Deoxyribonuclease I