Positive intergenic feedback circuitry, involving EBF1 and FOXO1, orchestrates B-cell fate
(2012) In Proceedings of the National Academy of Sciences 109(51). p.21028-21033- Abstract
- Recent studies have identified a number of transcriptional regulators, including E2A, early B-cell factor 1 (EBF1), FOXO1, and paired box gene 5 (PAX5), that promote early B-cell development. However, how this ensemble of regulators mechanistically promotes B-cell fate remains poorly understood. Here we demonstrate that B-cell development in FOXO1-deficient mice is arrested in the common lymphoid progenitor (CLP) LY6D(+) cell stage. We demonstrate that this phenotype closely resembles the arrest in B-cell development observed in EBF1-deficient mice. Consistent with these observations, we find that the transcription signatures of FOXO1- and EBF1-deficient LY6D(+) progenitors are strikingly similar, indicating a common set of target genes.... (More)
- Recent studies have identified a number of transcriptional regulators, including E2A, early B-cell factor 1 (EBF1), FOXO1, and paired box gene 5 (PAX5), that promote early B-cell development. However, how this ensemble of regulators mechanistically promotes B-cell fate remains poorly understood. Here we demonstrate that B-cell development in FOXO1-deficient mice is arrested in the common lymphoid progenitor (CLP) LY6D(+) cell stage. We demonstrate that this phenotype closely resembles the arrest in B-cell development observed in EBF1-deficient mice. Consistent with these observations, we find that the transcription signatures of FOXO1- and EBF1-deficient LY6D(+) progenitors are strikingly similar, indicating a common set of target genes. Furthermore, we found that depletion of EBF1 expression in LY6D(+) CLPs severely affects FOXO1 mRNA abundance, whereas depletion of FOXO1 activity in LY6D(+) CLPs ablates EBF1 transcript levels. We generated a global regulatory network from EBF1 and FOXO1 genome-wide transcription factor occupancy and transcription signatures derived from EBF1- and FOXO1-deficient CLPs. This analysis reveals that EBF1 and FOXO1 act in a positive feedback circuitry to promote and stabilize specification to the B-cell lineage. (Less)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/3481617
- author
- Mansson, Robert ; Welinder, Eva LU ; Ahsberg, Josefine ; Lin, Yin C. ; Benner, Christopher ; Glass, Christopher K. ; Lucas, Joseph S. ; Sigvardsson, Mikael and Murre, Cornelis
- organization
- publishing date
- 2012
- type
- Contribution to journal
- publication status
- published
- subject
- in
- Proceedings of the National Academy of Sciences
- volume
- 109
- issue
- 51
- pages
- 21028 - 21033
- publisher
- National Academy of Sciences
- external identifiers
-
- wos:000313123700059
- scopus:84871390259
- pmid:23213261
- ISSN
- 1091-6490
- DOI
- 10.1073/pnas.1211427109
- language
- English
- LU publication?
- yes
- id
- 8826ec9a-b483-4fc5-99eb-29cbed0bd1bb (old id 3481617)
- date added to LUP
- 2016-04-01 10:50:52
- date last changed
- 2022-03-27 20:04:09
@article{8826ec9a-b483-4fc5-99eb-29cbed0bd1bb,
abstract = {{Recent studies have identified a number of transcriptional regulators, including E2A, early B-cell factor 1 (EBF1), FOXO1, and paired box gene 5 (PAX5), that promote early B-cell development. However, how this ensemble of regulators mechanistically promotes B-cell fate remains poorly understood. Here we demonstrate that B-cell development in FOXO1-deficient mice is arrested in the common lymphoid progenitor (CLP) LY6D(+) cell stage. We demonstrate that this phenotype closely resembles the arrest in B-cell development observed in EBF1-deficient mice. Consistent with these observations, we find that the transcription signatures of FOXO1- and EBF1-deficient LY6D(+) progenitors are strikingly similar, indicating a common set of target genes. Furthermore, we found that depletion of EBF1 expression in LY6D(+) CLPs severely affects FOXO1 mRNA abundance, whereas depletion of FOXO1 activity in LY6D(+) CLPs ablates EBF1 transcript levels. We generated a global regulatory network from EBF1 and FOXO1 genome-wide transcription factor occupancy and transcription signatures derived from EBF1- and FOXO1-deficient CLPs. This analysis reveals that EBF1 and FOXO1 act in a positive feedback circuitry to promote and stabilize specification to the B-cell lineage.}},
author = {{Mansson, Robert and Welinder, Eva and Ahsberg, Josefine and Lin, Yin C. and Benner, Christopher and Glass, Christopher K. and Lucas, Joseph S. and Sigvardsson, Mikael and Murre, Cornelis}},
issn = {{1091-6490}},
language = {{eng}},
number = {{51}},
pages = {{21028--21033}},
publisher = {{National Academy of Sciences}},
series = {{Proceedings of the National Academy of Sciences}},
title = {{Positive intergenic feedback circuitry, involving EBF1 and FOXO1, orchestrates B-cell fate}},
url = {{http://dx.doi.org/10.1073/pnas.1211427109}},
doi = {{10.1073/pnas.1211427109}},
volume = {{109}},
year = {{2012}},
}