The Transcription Factor E4bp4/Nfil3 Controls Commitment to the NK Lineage and Directly Regulates Eomes and Id2 Expression

Overview

Journal J Exp Med

Specialties Allergy & Immunology
General Medicine

Date 2014 Mar 26

PMID 24663216

Citations 107

Authors

Victoria Male

Ilaria Nisoli

Tomasz Kostrzewski

David S J Allan

James R Carlyle

Graham M Lord

Andreas Wack

Hugh J M Brady

Affiliations

Soon will be listed here.

Abstract

The transcription factor E4bp4 (Nfil3) is essential for natural killer (NK) cell production. Here, we show that E4bp4 is required at the NK lineage commitment point when NK progenitors develop from common lymphoid progenitors (CLPs) and that E4bp4 must be expressed at the CLP stage for differentiation toward the NK lineage to occur. To elucidate the mechanism by which E4bp4 promotes NK development, we identified a central core of transcription factors that can rescue NK production from E4bp4(-/-) progenitors, suggesting that they act downstream of E4bp4. Among these were Eomes and Id2, which are expressed later in development than E4bp4. E4bp4 binds directly to the regulatory regions of both Eomes and Id2, promoting their transcription. We propose that E4bp4 is required for commitment to the NK lineage and promotes NK development by directly regulating the expression of the downstream transcription factors Eomes and Id2.

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