Recombination and transcription of the endogenous Ig heavy chain locus is effected by the Ig heavy chain intronic enhancer core region in the absenceof the matrix attachment regions
E. Sakai et al., Recombination and transcription of the endogenous Ig heavy chain locus is effected by the Ig heavy chain intronic enhancer core region in the absenceof the matrix attachment regions, P NAS US, 96(4), 1999, pp. 1526-1531
Citations number
69
Categorie Soggetti
Multidisciplinary
Journal title
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
The intronic Ig heavy chain (IgH) enhancer, which consists of the core enha
ncer flanked by 5' and 3' matrix attachment regions, has been implicated in
control of IgH locus recombination and transcription. To elucidate the reg
ulatory functions of the core enhancer and its associated matrix: attachmen
t regions in the endogenous IgH lotus, we have introduced targeted deletion
s of these elements, both individually and in combination, into an IgH(a/b)
-heterozygous embryonic stem cell line. These embryonic stem cells sere use
d to generate chimeric mice by recombination activating gene-2 (Rag-2)-defi
cient blastocyst complementation, and the effects of the introduced mutatio
ns were assayed in mutant B cells. We find that the core enhancer is necess
ary and sufficient to promote normal variable (V), diversity (D), and joini
ng (J) segment recombination in developing B lineage cells and IgH locus tr
anscription in mature B cells. Surprisingly, the 5' and 3' matrix attachmen
t regions were dispensable for these processes.