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

Abstract PAX5 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 expr...

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Autores principales: Charles E. Bullerwell, Philippe Pierre Robichaud, Pierre M. L. Deprez, Andrew P. Joy, Gabriel Wajnberg, Darwin D’Souza, Simi Chacko, Sébastien Fournier, Nicolas Crapoulet, David A. Barnett, Stephen M. Lewis, Rodney J. Ouellette
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Publicado: Nature Portfolio 2021
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spelling oai:doaj.org-article:5b11cbd215904b91952bccb6c01327a72021-12-02T15:23:02ZEBF1 drives hallmark B cell gene expression by enabling the interaction of PAX5 with the MLL H3K4 methyltransferase complex10.1038/s41598-021-81000-52045-2322https://doaj.org/article/5b11cbd215904b91952bccb6c01327a72021-01-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-81000-5https://doaj.org/toc/2045-2322Abstract PAX5 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.Charles E. BullerwellPhilippe Pierre RobichaudPierre M. L. DeprezAndrew P. JoyGabriel WajnbergDarwin D’SouzaSimi ChackoSébastien FournierNicolas CrapouletDavid A. BarnettStephen M. LewisRodney J. OuelletteNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-14 (2021)
institution DOAJ
collection DOAJ
language EN
topic Medicine
R
Science
Q
spellingShingle Medicine
R
Science
Q
Charles E. Bullerwell
Philippe Pierre Robichaud
Pierre M. L. Deprez
Andrew P. Joy
Gabriel Wajnberg
Darwin D’Souza
Simi Chacko
Sébastien Fournier
Nicolas Crapoulet
David A. Barnett
Stephen M. Lewis
Rodney J. Ouellette
EBF1 drives hallmark B cell gene expression by enabling the interaction of PAX5 with the MLL H3K4 methyltransferase complex
description Abstract PAX5 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.
format article
author Charles E. Bullerwell
Philippe Pierre Robichaud
Pierre M. L. Deprez
Andrew P. Joy
Gabriel Wajnberg
Darwin D’Souza
Simi Chacko
Sébastien Fournier
Nicolas Crapoulet
David A. Barnett
Stephen M. Lewis
Rodney J. Ouellette
author_facet Charles E. Bullerwell
Philippe Pierre Robichaud
Pierre M. L. Deprez
Andrew P. Joy
Gabriel Wajnberg
Darwin D’Souza
Simi Chacko
Sébastien Fournier
Nicolas Crapoulet
David A. Barnett
Stephen M. Lewis
Rodney J. Ouellette
author_sort Charles E. Bullerwell
title EBF1 drives hallmark B cell gene expression by enabling the interaction of PAX5 with the MLL H3K4 methyltransferase complex
title_short EBF1 drives hallmark B cell gene expression by enabling the interaction of PAX5 with the MLL H3K4 methyltransferase complex
title_full EBF1 drives hallmark B cell gene expression by enabling the interaction of PAX5 with the MLL H3K4 methyltransferase complex
title_fullStr EBF1 drives hallmark B cell gene expression by enabling the interaction of PAX5 with the MLL H3K4 methyltransferase complex
title_full_unstemmed EBF1 drives hallmark B cell gene expression by enabling the interaction of PAX5 with the MLL H3K4 methyltransferase complex
title_sort ebf1 drives hallmark b cell gene expression by enabling the interaction of pax5 with the mll h3k4 methyltransferase complex
publisher Nature Portfolio
publishDate 2021
url https://doaj.org/article/5b11cbd215904b91952bccb6c01327a7
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