scholarly journals EBF1 drives hallmark B cell gene expression by enabling the interaction of PAX5 with the MLL H3K4 methyltransferase complex

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Charles E. Bullerwell ◽  
Philippe Pierre Robichaud ◽  
Pierre M. L. Deprez ◽  
Andrew P. Joy ◽  
Gabriel Wajnberg ◽  
...  

AbstractPAX5 and EBF1 work synergistically to regulate genes that are involved in B lymphocyte differentiation. We used the KIS-1 diffuse large B cell lymphoma cell line, which is reported to have elevated levels of PAX5 expression, to investigate the mechanism of EBF1- and PAX5-regulated gene expression. We demonstrate the lack of expression of hallmark B cell genes, including CD19, CD79b, and EBF1, in the KIS-1 cell line. Upon restoration of EBF1 expression we observed activation of CD19, CD79b and other genes with critical roles in B cell differentiation. Mass spectrometry analyses of proteins co-immunoprecipitated with PAX5 in KIS-1 identified components of the MLL H3K4 methylation complex, which drives histone modifications associated with transcription activation. Immunoblotting showed a stronger association of this complex with PAX5 in the presence of EBF1. Silencing of KMT2A, the catalytic component of MLL, repressed the ability of exogenous EBF1 to activate transcription of both CD19 and CD79b in KIS-1 cells. We also find association of PAX5 with the MLL complex and decreased CD19 expression following silencing of KMT2A in other human B cell lines. These data support an important role for the MLL complex in PAX5-mediated transcription regulation.

Blood ◽  
1995 ◽  
Vol 85 (7) ◽  
pp. 1836-1842 ◽  
Author(s):  
MY Mapara ◽  
K Bommert ◽  
RC Bargou ◽  
C Leng ◽  
C Beck ◽  
...  

Recently G alpha 16, a new guanosine triphosphate (GTP) binding protein alpha subunit has been described to be specifically expressed in human hematopoietic cells. Expression of G alpha 16 was observed in human cell lines of myelomonocytic and T-lymphocytic origin, but not in human B-cell lines Raji and IM9. We studied the expression of G alpha 16 in human B cells corresponding to different stages of B-cell differentiation by means of reverse transcriptase-polymerase chain reaction (RT-PCR) and Western blotting. The human Burkitt's lymphoma cell lines Raji, Ramos, BJAB, the lymphoblastoid cell line SKW6.4, and the plasmocytoma cell line U266 were devoid of G alpha 16. In contrast, G alpha 16 was detected in the human progenitor B cell lines Reh and Nalm-6. Using the mu+, k-cell line BLIN-1 (pre-B cell phenotype) and its derived subclone 1E8 (surface mu+, k+; B-cell phenotype) G alpha 16 expression was found to disappear on transition from pre-B to B-cell differentiation stage. The analysis of a broad panel of human neoplastic B lymphocytes ranging from progenitor B-acute lymphatic leukemia (pre-pre-B-ALL), common acute leukemias (cALL), pre-B-ALL, mature B-ALL to low grade B-cell lymphoma (chronic lymphocytic leukemia of B-cell type, leukemic centrocytic non-Hodgkins lymphoma [NHL], hairy cell leukemia) showed that G alpha 16 expression is limited to progenitor and pre-B-ALL cells. Therefore, we conclude that within B-cell differentiation, G alpha 16 is expressed solely during early B cell ontogeny and downregulated during differentiation. Thus, G alpha 16 might be an important regulator involved in signaling processes in progenitor B cells.


2018 ◽  
Vol 192 (1) ◽  
pp. 68-81 ◽  
Author(s):  
A. L. Benko ◽  
C. A. McAloose ◽  
P. M. Becker ◽  
D. Wright ◽  
T. Sunyer ◽  
...  

Blood ◽  
2002 ◽  
Vol 99 (7) ◽  
pp. 2285-2290 ◽  
Author(s):  
James Z. Huang ◽  
Warren G. Sanger ◽  
Timothy C. Greiner ◽  
Louis M. Staudt ◽  
Dennis D. Weisenburger ◽  
...  

Recently we have identified subgroups of de novo primary diffuse large B-cell lymphoma (DLBCL) based on complementary DNA microarray-generated gene expression profiles. To correlate the gene expression profiles with cytogenetic abnormalities in these DLBCLs, we examined the occurrence of the t(14;18)(q32;q21) in the 2 distinctive subgroups of DLBCL: one with the germinal center B-cell gene expression signature and the other with the activated B cell–like gene expression signature. The t(14;18) was detected in 7 of 35 cases (20%). All 7 t(14;18)-positive cases had a germinal center B-cell gene expression profile, representing 35% of the cases in this subgroup, and 6 of these 7 cases had very similar gene expression profiles. The expression of bcl-2 and bcl-6 proteins was not significantly different between the t(14;18)-positive and -negative cases, whereas CD10 was detected only in the group with the germinal center B-cell expression profile, and CD10 was most frequently expressed in the t(14;18)-positive cases. This study supports the validity of subdividing DLBCL into 2 major subgroups by gene expression profiling, with the t(14;18) being an important event in the pathogenesis of a subset of DLBCL arising from germinal center B cells. CD10 protein expression is useful in identifying cases of DLBCL with a germinal center B-cell gene expression profile and is often expressed in cases with the t(14;18).


2013 ◽  
Vol 243 (1) ◽  
pp. 145-158 ◽  
Author(s):  
Mona Hassawi ◽  
Elena A. Shestakova ◽  
Marilaine Fournier ◽  
Charles-Étienne Lebert-Ghali ◽  
Gratianne Vaisson ◽  
...  

Blood ◽  
2015 ◽  
Vol 125 (14) ◽  
pp. 2228-2238 ◽  
Author(s):  
Jiun-Han Lin ◽  
Ju-Yin Lin ◽  
Ya-Ching Chou ◽  
Mei-Ru Chen ◽  
Te-Huei Yeh ◽  
...  

Key PointsEBV LMP2A alters B-cell gene expression; E47 and PU.1 are repressed by LMP2A, resulting in downregulation of MHC class II expression.


1988 ◽  
Vol 28 (4) ◽  
pp. 481-486 ◽  
Author(s):  
E. HoGBOM ◽  
I.-L. MARTENSSON ◽  
K. FUNA ◽  
T. LEANDERSON

PLoS ONE ◽  
2013 ◽  
Vol 8 (6) ◽  
pp. e66833 ◽  
Author(s):  
Jane H. Kinnaird ◽  
William Weir ◽  
Zeeshan Durrani ◽  
Sreerekha S. Pillai ◽  
Margaret Baird ◽  
...  

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