The transcription factors E2A and HEB act in concert to induce the expression of FOXO1 in the common lymphoid progenitor
(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:
https://lup.lub.lu.se/record/2211653
- author
- Welinder, Eva LU ; Mansson, Robert ; Mercer, Elinore M. ; Bryder, David LU ; Sigvardsson, Mikael and Murre, Cornelis
- organization
- publishing date
- 2011
- 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 Academy of Sciences
- external identifiers
-
- wos:000295975300039
- scopus:80054805278
- pmid:21972416
- ISSN
- 1091-6490
- DOI
- 10.1073/pnas.1111766108
- language
- English
- LU publication?
- yes
- additional info
- The information about affiliations in this record was updated in December 2015. The record was previously connected to the following departments: Connective Tissue Biology (013230151), Immunology (013212020)
- id
- 0f96b450-d7f7-44ff-8c7a-9485f759578c (old id 2211653)
- date added to LUP
- 2016-04-01 10:56:27
- date last changed
- 2022-02-25 07:03:33
@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 Academy of 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}}, doi = {{10.1073/pnas.1111766108}}, volume = {{108}}, year = {{2011}}, }