A complex chromatin landscape revealed by patterns of nuclease sensitivity and histone modification within the mouse beta-globin locus.
In order to create an extended map of chromatin features within a mammalian multigene locus, we have determined the extent of nuclease sensitivity and the pattern of histone modifications associated with the mouse beta-globin genes in adult erythroid tissue. We show that the nuclease-sensitive domain encompasses the beta-globin genes along with several flanking olfactory receptor genes that are inactive in erythroid cells. We describe enhancer-blocking or boundary elements on either side of the locus that are bound in vivo by the transcription factor CTCF, but we found that they do not coincide with transitions in nuclease sensitivity flanking the locus or with patterns of histone modifications within it. In addition, histone hyperacetylation and dimethylation of histone H3 K4 are not uniform features of the nuclease-sensitive mouse beta-globin domain but rather define distinct subdomains within it. Our results reveal a complex chromatin landscape for the active beta-globin locus and illustrate the complexity of broad structural changes that accompany gene activation.
Bulger
Michael
M
Division of Basic Sciences, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA.
Schübeler
Dirk
D
Bender
M A
MA
Hamilton
Joan
J
Farrell
Catherine M
CM
Hardison
Ross C
RC
Groudine
Mark
M
D000818:Animals; D001483:Base Sequence; D001665:Binding Sites; D015139:Blotting, Southern; D000076246:CCCTC-Binding Factor; D002467:Cell Nucleus / Q000378:metabolism; D002645:Chickens; D002843:Chromatin / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000378:metabolism; D003851:Deoxyribonucleases / Q000378:metabolism*; D004912:Erythrocytes / Q000378:metabolism; D005914:Globins / Q000235:genetics* / Q000378:metabolism; D006657:Histones / Q000378:metabolism*; D006801:Humans; D020014:K562 Cells; D051379:Mice; D008957:Models, Genetic; D008969:Molecular Sequence Data; D011233:Precipitin Tests; D017434:Protein Structure, Tertiary; D012097:Repressor Proteins; D013154:Spleen / Q000378:metabolism; D014157:Transcription Factors / Q000378:metabolism
D000076246:CCCTC-Binding Factor; C000619697:CTCF protein, human; D002843:Chromatin; C000619698:Ctcf protein, mouse; D004268:DNA-Binding Proteins; D006657:Histones; D012097:Repressor Proteins; D014157:Transcription Factors; D005914:Globins; D003851:Deoxyribonucleases