Regulation of immunoglobulin promoter activity by TFII-I class transcription factors.
The restriction of immunoglobulin variable region promoter activity to B lymphocytes is a well known paradigm of promoter specificity. Recently, a cis-element, located downstream of the transcription initiation site of murine heavy chain variable promoters, was shown to be critical for B cell activity and specificity. Here we show that mutation of this element, termed DICE (Downstream Immunoglobulin Control Element), reduces in vivo activity in B cells. Gel mobility shift assays show that DICE forms B cell-specific complexes that were also sensitive to DICE mutation. DICE mutation strongly reduces the ability of a distal immunoglobulin heavy chain intronic enhancer to stimulate transcription. We also identify a DICE-interacting factor: a TFII-I-related protein known as BEN (also termed Mus-TRD1 and WBSCR11). Dominant-negative and RNAi-mediated knockdown experiments indicate that BEN can both positively and negatively regulate IgH promoter activity, depending on the cell line.
Tantin
Dean
D
Department of Biology and Center for Cancer Research, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139-4307, USA.
Tussie-Luna
Maria Isabel
MI
Roy
Ananda L
AL
Sharp
Phillip A
PA
D000818:Animals; D001402:B-Lymphocytes / Q000378:metabolism; D001483:Base Sequence; D015153:Blotting, Western; D019556:COS Cells; D002460:Cell Line; D002467:Cell Nucleus / Q000378:metabolism; D004591:Electrophoresis, Polyacrylamide Gel; D004742:Enhancer Elements, Genetic; D005786:Gene Expression Regulation; D005803:Genes, Immunoglobulin / Q000235:genetics; D007143:Immunoglobulin Heavy Chains / Q000378:metabolism; D007136:Immunoglobulins / Q000235:genetics*; D007438:Introns; D013058:Mass Spectrometry; D051379:Mice; D008863:Microspheres; D008969:Molecular Sequence Data; D009124:Muscle Proteins / Q000737:chemistry / Q000502:physiology*; D009154:Mutation; D009687:Nuclear Proteins / Q000737:chemistry / Q000502:physiology*; D010957:Plasmids / Q000378:metabolism; D011233:Precipitin Tests; D011401:Promoter Regions, Genetic; D034622:RNA Interference; D012333:RNA, Messenger / Q000378:metabolism; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; D015534:Trans-Activators / Q000737:chemistry / Q000502:physiology*; D019473:Transcription Factors, TFII / Q000737:chemistry* / Q000502:physiology; D014158:Transcription, Genetic; D014162:Transfection
C486330:Gtf2i protein, mouse; C486558:Gtf2ird1 protein, mouse; D007143:Immunoglobulin Heavy Chains; D007136:Immunoglobulins; D009124:Muscle Proteins; D009687:Nuclear Proteins; D012333:RNA, Messenger; D015534:Trans-Activators; D019473:Transcription Factors, TFII