TY - JOUR
T1 - Identification of 3α-hs4, a novel Ig heavy chain enhancer element regulated at multiple stages of B cell differentiation
AU - Michaelson, Jennifer S.
AU - Giannini, Sandra L.
AU - Birshtein, Barbara K.
N1 - Funding Information:
We thank Dr Mallika Singh for guidance in the transfection experiments. In addition, we thank Drs Mark Groudine and Linda Madisen for sharing their unpublished observations on hs3 and hs4 with us when we were compiling our manuscript. We further acknowledge Dr Matthew Scharff, Dr Nancy Green, Dr Fred Alt and Marc D. Michaelson for critical reading of the manuscript. This work was supported by Grants A113509 and PC30CA13330 from the National Institutes of Health (BKB). JSM was supported by a Howard Hughes Medical Institute predoctoral fellowship (9-526-4653). SLG was supported by Training Grant CA09173 from the National Institutes of Health.
PY - 1995/3/25
Y1 - 1995/3/25
N2 - In addition to Eμ, several elements downstream of the IgH cluster, i.e. 3' of the Cα gene, areinvolved in regulating IgH gene rearrangement and expression. This entire downstream regulatory region was shown to be deleted in the mutant myeloma cell line, LP1.2. The deletion encompasses ∼34 kb and is presumably responsible for the reduced levels of IgH expression in this cell line. An additional regulatory element, included in the LP1.2 deletion, was identified by investigation of a DNase I hypersensitivity site located -.33 kb downstream of the α gene and present in pre-B and plasma cells. This novel IgH gene enhancer element, termed 3'α-hs4, is capable of activity through out B cell development. Transient transfectlon of 3'α-hs4 in a CAT reporter gene construct shows transcriptional enhancement activity approximating that of Eμ in S194 plasmacytoma and M12.4.1 and A-20 B cell lines; while in apre-B cell line, 18-81, the average activity is 25% that of Eμ. Enhancer activity was localized to an800 bp fragment. The activity of 3'α-hs4 is orientation independent and appears to be B cell specific. Tight regulation of 3'α-hs4 is inferred from its variable activity in different plasmacytoma cell lines and within the pie B cell line, 18-81.
AB - In addition to Eμ, several elements downstream of the IgH cluster, i.e. 3' of the Cα gene, areinvolved in regulating IgH gene rearrangement and expression. This entire downstream regulatory region was shown to be deleted in the mutant myeloma cell line, LP1.2. The deletion encompasses ∼34 kb and is presumably responsible for the reduced levels of IgH expression in this cell line. An additional regulatory element, included in the LP1.2 deletion, was identified by investigation of a DNase I hypersensitivity site located -.33 kb downstream of the α gene and present in pre-B and plasma cells. This novel IgH gene enhancer element, termed 3'α-hs4, is capable of activity through out B cell development. Transient transfectlon of 3'α-hs4 in a CAT reporter gene construct shows transcriptional enhancement activity approximating that of Eμ in S194 plasmacytoma and M12.4.1 and A-20 B cell lines; while in apre-B cell line, 18-81, the average activity is 25% that of Eμ. Enhancer activity was localized to an800 bp fragment. The activity of 3'α-hs4 is orientation independent and appears to be B cell specific. Tight regulation of 3'α-hs4 is inferred from its variable activity in different plasmacytoma cell lines and within the pie B cell line, 18-81.
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U2 - 10.1093/nar/23.6.975
DO - 10.1093/nar/23.6.975
M3 - Article
C2 - 7731812
AN - SCOPUS:0028988293
SN - 0305-1048
VL - 23
SP - 975
EP - 981
JO - Nucleic acids research
JF - Nucleic acids research
IS - 6
ER -