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

Research output: Contribution to journalArticle

Standard

The transcription factors E2A and HEB act in concert to induce the expression of FOXO1 in the common lymphoid progenitor. / Welinder, Eva; Mansson, Robert; Mercer, Elinore M.; Bryder, David; Sigvardsson, Mikael; Murre, Cornelis.

In: Proceedings of the National Academy of Sciences, Vol. 108, No. 42, 2011, p. 17402-17407.

Research output: Contribution to journalArticle

Harvard

APA

CBE

MLA

Vancouver

Author

Welinder, Eva ; Mansson, Robert ; Mercer, Elinore M. ; Bryder, David ; Sigvardsson, Mikael ; Murre, Cornelis. / The transcription factors E2A and HEB act in concert to induce the expression of FOXO1 in the common lymphoid progenitor. In: Proceedings of the National Academy of Sciences. 2011 ; Vol. 108, No. 42. pp. 17402-17407.

RIS

TY - JOUR

T1 - The transcription factors E2A and HEB act in concert to induce the expression of FOXO1 in the common lymphoid progenitor

AU - Welinder, Eva

AU - Mansson, Robert

AU - Mercer, Elinore M.

AU - Bryder, David

AU - Sigvardsson, Mikael

AU - Murre, Cornelis

N1 - 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)

PY - 2011

Y1 - 2011

N2 - 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.

AB - 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.

U2 - 10.1073/pnas.1111766108

DO - 10.1073/pnas.1111766108

M3 - Article

VL - 108

SP - 17402

EP - 17407

JO - Proceedings of the National Academy of Sciences

JF - Proceedings of the National Academy of Sciences

SN - 1091-6490

IS - 42

ER -