An Erg-driven transcriptional program controls B cell lymphopoiesis
Open Access
- 15 June 2020
- journal article
- research article
- Published by Springer Science and Business Media LLC in Nature Communications
- Vol. 11 (1), 1-14
- https://doi.org/10.1038/s41467-020-16828-y
Abstract
B lymphoid development is initiated by the differentiation of hematopoietic stem cells into lineage committed progenitors, ultimately generating mature B cells. This highly regulated process generates clonal immunological diversity via recombination of immunoglobulin V, D and J gene segments. While several transcription factors that control B cell development and V(D)J recombination have been defined, how these processes are initiated and coordinated into a precise regulatory network remains poorly understood. Here, we show that the transcription factor ETS Related Gene (Erg) is essential for early B lymphoid differentiation. Erg initiates a transcriptional network involving the B cell lineage defining genes, Ebf1 and Pax5, which directly promotes expression of key genes involved in V(D)J recombination and formation of the B cell receptor. Complementation of Erg deficiency with a productively rearranged immunoglobulin gene rescued B lineage development, demonstrating that Erg is an essential and stage-specific regulator of the gene regulatory network controlling B lymphopoiesis.This publication has 76 references indexed in Scilit:
- An integrated encyclopedia of DNA elements in the human genomeNature, 2012
- DNA Sequence-Dependent Compartmentalization and Silencing of Chromatin at the Nuclear LaminaCell, 2012
- Dynamic Transformations of Genome-wide Epigenetic Marking and Transcriptional Control Establish T Cell IdentityCell, 2012
- Two Forms of Loops Generate the Chromatin Conformation of the Immunoglobulin Heavy-Chain Gene LocusCell, 2011
- A conditional knockout resource for the genome-wide study of mouse gene functionNature, 2011
- A global network of transcription factors, involving E2A, EBF1 and Foxo1, that orchestrates B cell fateNature Immunology, 2010
- Role of STAT5 in controlling cell survival and immunoglobulin gene recombination during pro-B cell developmentNature Immunology, 2009
- Chapter 1 Cis‐Regulatory Elements and Epigenetic Changes Control Genomic Rearrangements of the IgH LocusAdvances in Immunology, 2008
- Regulation of B cell fate commitment and immunoglobulin heavy-chain gene rearrangements by IkarosNature Immunology, 2008
- Foxo1 directly regulates the transcription of recombination-activating genes during B cell developmentNature Immunology, 2008