Gene expression analysis to identify Klf2 target genes in B-cell progenitors [+Klf2]

ABSTRACT: The sequential activation of distinct developmental gene networks governs the ultimate identity of a cell, but the mechanisms by which downstream programs are activated are incompletely understood. The preB-cell receptor (preBCR) is an important checkpoint of B-cell development and essential for a preB-cell to traverse into an immature B-cell. Here, we show that activation of Mef2 transcription factors by preBCR is necessary for initiating the subsequent genetic network. We demonstrate that B-cell development is blocked at the preB-cell stage in mice deficient for Mef2c and Mef2d transcription factors and that preBCR 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. RNA-seq experiments were performed from Klf2 overexpressing BMiFLT3 (15-3) cells to identify genes regulated by Klf2

ORGANISM(S): Mus musculus

SUBMITTER: Julia Herglotz 

PROVIDER: E-GEOD-73559 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress