The beta-globin LCR is not necessary for an open chromatin structure or developmentally regulated transcription of the native mouse beta-globin locus.
The murine beta-globin locus control region (LCR) was deleted from its native chromosomal location. The approximately 25 kb deletion eliminates all sequences and structures homologous to those defined as the human LCR. In differentiated ES cells and erythroleukemia cells containing the LCR-deleted chromosome, DNasel sensitivity of the beta-globin domain is established and maintained, developmental regulation of the locus is intact, and beta-like globin RNA levels are reduced 5%-25% of normal. Thus, in the native murine beta-globin locus, the LCR is necessary for normal levels of transcription, but other elements are sufficient to establish the open chromatin structure, transcription, and developmental specificity of the locus. These findings suggest a contributory rather than dominant function for the LCR in its native location.
Epner
E
E
Division of Basic Sciences, Fred Hutchinson Cancer Research Center, Seattle, Washington 98109, USA.
Reik
A
A
Cimbora
D
D
Telling
A
A
Bender
M A
MA
Fiering
S
S
Enver
T
T
Martin
D I
DI
Kennedy
M
M
Keller
G
G
Groudine
M
M
D000818:Animals; D002843:Chromatin / Q000502:physiology*; D003851:Deoxyribonucleases; D017353:Gene Deletion; D015870:Gene Expression / Q000502:physiology; D005914:Globins / Q000737:chemistry / Q000235:genetics*; D006801:Humans; D004915:Leukemia, Erythroblastic, Acute; D051379:Mice; D010641:Phenotype; D011487:Protein Conformation; D017434:Protein Structure, Tertiary; D015533:Transcriptional Activation / Q000502:physiology*; D014407:Tumor Cells, Cultured / Q000737:chemistry / Q000502:physiology
D002843:Chromatin; D005914:Globins; D003851:Deoxyribonucleases