The beta-globin HS4 insulator confers copy-number dependent expression of IgH regulatory elements in stable B cell transfectants.
Locus control regions (LCR) were first defined by their theoretical ability to enhance the expression of linked genes in a tissue-specific, position-independent and copy-number dependent manner. In fact, few of the so-called LCR identified completely fulfil this definition. For example, the regulatory elements located in 5' (Emu) and 3' (HS3a; HS1,2; HS3b; HS4) of the IgH locus display some properties of a LCR but lack a copy-number dependence and sometimes display position effects in transgenes. In order to study whether addition of insulators would allow to overcome such problems in transgenes, we studied constructs harboring a V(H) promoter-green fluorescent protein reporter gene linked to the 3' and/or 5' IgH elements, surrounded or not with the chicken beta-globin 5'HS4 insulator. When flanked with insulators it appeared that either 3' IgH and 5' IgH regulatory elements now behave as true LCR elements and noticeably display copy-number dependence in transfected pre-B or B cell lines.
Guglielmi
Laurence
L
UMR CNRS 6101, Faculté de Médecine, 2 rue Dr Marcland, 87025, Limoges, France.
Truffinet
Véronique
V
Cogné
Michel
M
Denizot
Yves
Y
D001402:B-Lymphocytes / Q000378:metabolism*; D018628:Gene Dosage; D005786:Gene Expression Regulation; D005809:Genes, Regulator; D005914:Globins / Q000235:genetics*; D006801:Humans; D007143:Immunoglobulin Heavy Chains / Q000235:genetics* / Q000378:metabolism; D017422:Sequence Analysis, DNA; D014162:Transfection
D007143:Immunoglobulin Heavy Chains; D005914:Globins