scholarly journals Interaction between the immunoglobulin heavy chain 3′ regulatory region and the IgH transcription unit during B cell differentiation

2011 ◽  
Vol 49 (1-2) ◽  
pp. 297-303 ◽  
Author(s):  
Zhongliang Ju ◽  
Sanjukta Chatterjee ◽  
Barbara K. Birshtein
1990 ◽  
Vol 10 (3) ◽  
pp. 1076-1083
Author(s):  
B Porton ◽  
D M Zaller ◽  
R Lieberson ◽  
L A Eckhardt

The immunoglobulin heavy-chain (IgH) enhancer serves to activate efficient and accurate transcription of cloned IgH genes when introduced into B lymphomas or myelomas. The role of this enhancer after gene activation, however, is unclear. The endogenous IgH genes in several cell lines, for example, have lost the IgH enhancer by deletion and yet continue to be expressed. This might be explained if the role of the enhancer were to establish high-level gene transcription but not to maintain it. Alternatively, other enhancers might lie adjacent to endogenous IgH genes, substituting their activity for that of the lost IgH enhancer. To address both of these alternatives, we searched for enhancer activity within the flanking regions of one of these IgH enhancer-independent genes and designed an experiment that allowed us to consider separately the establishment and maintenance of expression of a transfected gene. For the latter experiment we generated numerous pre-B cell lines stably transformed with a gamma 2a gene. In this gene, the IgH enhancer lay at a site outside the heavy-chain transcription unit, between DH and JH gene segments. After expression of the transfected gene was established, selective conditions were chosen for the outgrowth of subclones that had undergone D-J joining and thus IgH enhancer deletion. Measurements of gamma 2a expression before and after enhancer deletion revealed that the enhancer was required for maintenance of expression of the transfected gene. The implication of this finding for models of enhancer function in endogenous genes is discussed.


2018 ◽  
Vol 2 (3) ◽  
pp. 252-262 ◽  
Author(s):  
Nour Ghazzaui ◽  
Hussein Issaoui ◽  
Alexis Saintamand ◽  
Christelle Oblet ◽  
Claire Carrion ◽  
...  

Key Points Similar to B2 B cells, the IgH 3′RR superenhancer controls μ-chain transcription and cell fate in B1 B cells. In contrast to B2 B cells, deletion of the IgH 3′RR superenhancer affects B1 B-cell late repertoire diversity.


Blood ◽  
1998 ◽  
Vol 91 (2) ◽  
pp. 603-607 ◽  
Author(s):  
Weiyi Chen ◽  
Shinsuke Iida ◽  
Diane C. Louie ◽  
Riccardo Dalla-Favera ◽  
R.S.K. Chaganti

Abstract The BCL6 gene encodes a POZ/Zinc-finger protein, which acts as a sequence-specific transcriptional repressor. It is expressed in B cells within the germinal centers (GC) and is required for GC formation. In ≈40% of diffuse large cell lymphomas (DLCL) and ≈14% of follicular lymphomas (FL), the BCL6 gene is rearranged by chromosomal translocations, which juxtapose heterologous promoters and 5′ untranslated sequences derived from other chromosomes to the BCL6 coding domain or by mutations in the 5′ regulatory region. To understand the functional consequence of the chromosomal translocations, we have studied the patterns of expression of the promoters found juxtaposed to BCL6 in DLCL and FL during B-lineage differentiation. Distinct heterologous 5′ untranslated regions (IGH, IGL, TTF) were identified fused to the BCL6 coding domain by analysis ofBCL6 cDNAs in two DLCL cases and one mixed follicular lymphoma (MxFL). These three sequences, as well as three other previously identified BCL6 fusion partners (IGHG3, BOB1,H4), were studied for their pattern of expression during B-lineage differentiation by Northern blot analysis of B-cell lines representative of the pre-B, B, immunoblast, and plasma cell stages. In contrast to BCL6, whose transcription is activated only in B cells within the GC, all of the other sequences displayed a broader pattern of expression ranging from constitutive expression throughout B-cell differentiation to persistent expression in immunoblasts and plasma cells. These results indicate that the expression ofBCL6 is deregulated as a consequence of fusion to heterologous promoter regions. The persistent expression of activated BCL6may contribute to lymphomagenesis by blocking B-cell differentiation within the GC.


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