Advanced

The transcription factors E2A and HEB act in concert to induce the expression of FOXO1 in the common lymphoid progenitor

Welinder, Eva LU ; Mansson, Robert; Mercer, Elinore M.; Bryder, David LU ; Sigvardsson, Mikael and Murre, Cornelis (2011) In Proceedings of the National Academy of Sciences 108(42). p.17402-17407
Abstract
Recent studies have identified a number of transcriptional regulators, including E proteins, EBF1, FOXO1, and PAX5, that act together to orchestrate the B-cell fate. However, it still remains unclear as to how they are linked at the earliest stages of B-cell development. Here, we show that lymphocyte development in HEB-ablated mice exhibits a partial developmental arrest, whereas B-cell development in E2A(+/-)HEB(-/)-mice is completely blocked at the LY6D(-) common lymphoid progenitor stage. We show that the transcription signatures of E2A-and HEB-ablated common lymphoid progenitors significantly overlap. Notably, we found that Foxo1 expression was substantially reduced in the LY6D-HEB-and E2A-deficient cells. Finally, we show that E2A... (More)
Recent studies have identified a number of transcriptional regulators, including E proteins, EBF1, FOXO1, and PAX5, that act together to orchestrate the B-cell fate. However, it still remains unclear as to how they are linked at the earliest stages of B-cell development. Here, we show that lymphocyte development in HEB-ablated mice exhibits a partial developmental arrest, whereas B-cell development in E2A(+/-)HEB(-/)-mice is completely blocked at the LY6D(-) common lymphoid progenitor stage. We show that the transcription signatures of E2A-and HEB-ablated common lymphoid progenitors significantly overlap. Notably, we found that Foxo1 expression was substantially reduced in the LY6D-HEB-and E2A-deficient cells. Finally, we show that E2A binds to enhancer elements across the FOXO1 locus to activate Foxo1 expression, linking E2A and FOXO1 directly in a common pathway. In summary, the data indicate that the earliest event in B-cell specification involves the induction of FOXO1 expression and requires the combined activities of E2A and HEB. (Less)
Please use this url to cite or link to this publication:
author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Proceedings of the National Academy of Sciences
volume
108
issue
42
pages
17402 - 17407
publisher
National Acad Sciences
external identifiers
  • wos:000295975300039
  • scopus:80054805278
ISSN
1091-6490
DOI
10.1073/pnas.1111766108
language
English
LU publication?
yes
id
0f96b450-d7f7-44ff-8c7a-9485f759578c (old id 2211653)
date added to LUP
2011-12-01 08:30:02
date last changed
2017-07-30 03:24:19
@article{0f96b450-d7f7-44ff-8c7a-9485f759578c,
  abstract     = {Recent studies have identified a number of transcriptional regulators, including E proteins, EBF1, FOXO1, and PAX5, that act together to orchestrate the B-cell fate. However, it still remains unclear as to how they are linked at the earliest stages of B-cell development. Here, we show that lymphocyte development in HEB-ablated mice exhibits a partial developmental arrest, whereas B-cell development in E2A(+/-)HEB(-/)-mice is completely blocked at the LY6D(-) common lymphoid progenitor stage. We show that the transcription signatures of E2A-and HEB-ablated common lymphoid progenitors significantly overlap. Notably, we found that Foxo1 expression was substantially reduced in the LY6D-HEB-and E2A-deficient cells. Finally, we show that E2A binds to enhancer elements across the FOXO1 locus to activate Foxo1 expression, linking E2A and FOXO1 directly in a common pathway. In summary, the data indicate that the earliest event in B-cell specification involves the induction of FOXO1 expression and requires the combined activities of E2A and HEB.},
  author       = {Welinder, Eva and Mansson, Robert and Mercer, Elinore M. and Bryder, David and Sigvardsson, Mikael and Murre, Cornelis},
  issn         = {1091-6490},
  language     = {eng},
  number       = {42},
  pages        = {17402--17407},
  publisher    = {National Acad Sciences},
  series       = {Proceedings of the National Academy of Sciences},
  title        = {The transcription factors E2A and HEB act in concert to induce the expression of FOXO1 in the common lymphoid progenitor},
  url          = {http://dx.doi.org/10.1073/pnas.1111766108},
  volume       = {108},
  year         = {2011},
}