Beta-globin gene switching and DNase I sensitivity of the endogenous beta-globin locus in mice do not require the locus control region

Mol Cell. 2000 Feb;5(2):387-93. doi: 10.1016/s1097-2765(00)80433-5.

Abstract

We have generated mice with a targeted deletion of the beta-globin locus control region (LCR). Mice homozygous for the deletion die early in embryogenesis but can be rescued with a YAC containing the human beta-globin locus. After germline passage, deletion of the LCR leads to a severe reduction in expression of all mouse beta-like globin genes, but no alteration in the developmental specificity of expression. Furthermore, a DNase I-sensitive "open" chromatin conformation of the locus is established and maintained. Thus, the dominant role of the LCR in the native locus is to confer high-level transcription, and elements elsewhere in the locus are sufficient to establish and maintain an open conformation and to confer developmentally regulated globin gene expression.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Chromatin / ultrastructure*
  • Chromosomes, Artificial, Yeast
  • DNA Footprinting
  • Deoxyribonuclease I
  • Gene Expression Regulation, Developmental
  • Gene Rearrangement*
  • Globins / genetics*
  • Heterozygote
  • Humans
  • Locus Control Region*
  • Mice
  • Mice, Mutant Strains
  • Sequence Deletion
  • Thalassemia / genetics

Substances

  • Chromatin
  • Globins
  • Deoxyribonuclease I