Distinct Promoters Mediate the Regulation of <i>Ebf1</i> Gene Expression by Interleukin-7 and Pax5

Journal article

The E2A gene products, E12 and E47, are critical regulators of B cell development. However, it remains elusive whether E12 and E47 have overlapping and/or distinct functions during B lymphopoiesis. We have generated mice deficient for either E12 or E47 and examined their roles in B cell maturation. We show that E47 is essential for developmental progression at the prepro–B cell stage, whereas E12 is dispensable for early B cell development, commitment, and maintenance. In contrast, both E12 and E47 play critical roles in pre–B and immature B cells to promote immunoglobulin λ (Igλ) germline transcription as well as Igλ VJ gene rearrangement. Furthermore, we show that E12 as well as E47 is required to promote receptor editing upon exposure to self-antigen. We demonstrate that increasing levels of E12 and E47 act to induce Igλ germline transcription, promote trimethylated lysine 4 on histone 3 (H3) as well as H3 acetylation across the Jλ region, and activate Igλ VJ gene rearrangement. We propose that in the pre–B and immature B cell compartments, gradients of E12 and E47 activities are established to mechanistically regulate the sequential rearrangement of the Ig light chain genes

Authors: Roessler, S; Györy, I; Imhof, S; Spivakov, M; Williams, RR

• Publication status: Published
• Peer review status: Peer reviewed
• Publisher: Taylor and Francis Group
• Journal: Molecular and Cellular Biology
• Volume: 27
• Issue: 2
• Pages: 579-594
• Publication date: 2006-11-14
• DOI: 10.1128/mcb.01192-06
• EISSN: 1098-5549
• ISSN: 0270-7306
• Language: English
• Keywords: Transcription (linguistics); Promoter; ETS1; Gene; Gene isoform; Biology; Cell biology; Genetics; Regulation of gene expression; Transcription factor; PAX5; Function (biology); IRF4; Gene expression