Essential control of early B-cell development by Mef2 transcription factors
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Essential control of early B-cell development by Mef2 transcription factors. / Herglotz, Julia; Unrau, Ludmilla; Hauschildt, Friderike; Fischer, Meike; Kriebitzsch, Neele; Alawi, Malik; Indenbirken, Daniela; Spohn, Michael; Müller, Ursula; Ziegler, Marion; Schuh, Wolfgang; Jäck, Hans-Martin; Stocking, Carol.
In: BLOOD, Vol. 127, No. 5, 04.02.2016, p. 572-81.Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review
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TY - JOUR
T1 - Essential control of early B-cell development by Mef2 transcription factors
AU - Herglotz, Julia
AU - Unrau, Ludmilla
AU - Hauschildt, Friderike
AU - Fischer, Meike
AU - Kriebitzsch, Neele
AU - Alawi, Malik
AU - Indenbirken, Daniela
AU - Spohn, Michael
AU - Müller, Ursula
AU - Ziegler, Marion
AU - Schuh, Wolfgang
AU - Jäck, Hans-Martin
AU - Stocking, Carol
N1 - © 2016 by The American Society of Hematology.
PY - 2016/2/4
Y1 - 2016/2/4
N2 - The sequential activation of distinct developmental gene networks governs the ultimate identity of a cell, but the mechanisms involved in initiating downstream programs are incompletely understood. The pre-B-cell receptor (pre-BCR) is an important checkpoint of B-cell development and is essential for a pre-B cell to traverse into an immature B cell. Here, we show that activation of myocyte enhancer factor 2 (Mef2) transcription factors (TFs) by the pre-BCR is necessary for initiating the subsequent genetic network. We demonstrate that B-cell development is blocked at the pre-B-cell stage in mice deficient for Mef2c and Mef2d TFs and that pre-BCR signaling enhances the transcriptional activity of Mef2c/d through phosphorylation by the Erk5 mitogen-activating kinase. This activation is instrumental in inducing Krüppel-like factor 2 and several immediate early genes of the AP1 and Egr family. Finally, we show that Mef2 proteins cooperate with the products of their target genes (Irf4 and Egr2) to induce secondary waves of transcriptional regulation. Our findings uncover a novel role for Mef2c/d in coordinating the transcriptional network that promotes early B-cell development.
AB - The sequential activation of distinct developmental gene networks governs the ultimate identity of a cell, but the mechanisms involved in initiating downstream programs are incompletely understood. The pre-B-cell receptor (pre-BCR) is an important checkpoint of B-cell development and is essential for a pre-B cell to traverse into an immature B cell. Here, we show that activation of myocyte enhancer factor 2 (Mef2) transcription factors (TFs) by the pre-BCR is necessary for initiating the subsequent genetic network. We demonstrate that B-cell development is blocked at the pre-B-cell stage in mice deficient for Mef2c and Mef2d TFs and that pre-BCR signaling enhances the transcriptional activity of Mef2c/d through phosphorylation by the Erk5 mitogen-activating kinase. This activation is instrumental in inducing Krüppel-like factor 2 and several immediate early genes of the AP1 and Egr family. Finally, we show that Mef2 proteins cooperate with the products of their target genes (Irf4 and Egr2) to induce secondary waves of transcriptional regulation. Our findings uncover a novel role for Mef2c/d in coordinating the transcriptional network that promotes early B-cell development.
U2 - 10.1182/blood-2015-04-643270
DO - 10.1182/blood-2015-04-643270
M3 - SCORING: Journal article
C2 - 26660426
VL - 127
SP - 572
EP - 581
JO - BLOOD
JF - BLOOD
SN - 0006-4971
IS - 5
ER -
