Dataset Information

An anticlastogenic function for the Polycomb Group gene Bmi1.

ABSTRACT: BMI1 is a key component of multiprotein Polycomb repression complex 1 (PRC1), and its disruption in mice induces severe aplastic anemia by early adulthood. The contributing mechanisms responsible for this phenotype remain elusive. Here we show that transformed human cell lines as well as primitive hematopoietic cells exhibit a high frequency of spontaneous chromosome breaks upon BMI1 depletion and are hypersensitive to genotoxic agents. Consistent with these observations, we found that BMI1 is recruited rapidly to DNA damage foci where it blocks transcriptional elongation. We also show that BMI1 contributes to homologous recombination DNA repair and is required for checkpoint recovery. Taken together, our results suggest that BMI1 is critical for the maintenance of chromosome integrity in both normal and transformed cells.

SUBMITTER: Chagraoui J

PROVIDER: S-EPMC3069154 | biostudies-literature | 2011 Mar

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

An anticlastogenic function for the Polycomb Group gene Bmi1.

Chagraoui Jalila J Hébert Josée J Girard Simon S Sauvageau Guy G

Proceedings of the National Academy of Sciences of the United States of America 20110314 13

BMI1 is a key component of multiprotein Polycomb repression complex 1 (PRC1), and its disruption in mice induces severe aplastic anemia by early adulthood. The contributing mechanisms responsible for this phenotype remain elusive. Here we show that transformed human cell lines as well as primitive hematopoietic cells exhibit a high frequency of spontaneous chromosome breaks upon BMI1 depletion and are hypersensitive to genotoxic agents. Consistent with these observations, we found that BMI1 is r ...[more]

PMID: 21402923

Similar Datasets

Project description:Bmi1 is a component of the Polycomb-repressive complexes (PRC) and essential for maintaining the pool of adult stem cells. PRC are key regulators for embryonic development by modifying chromatin architecture and maintaining gene repression. To assess the role of Bmi1 in pluripotent stem cells and upon exit from pluripotency during differentiation, we studied forced Bmi1 expression in mouse embryonic stem cells (ESC). We found that ESC do not express detectable levels of Bmi1 RNA and protein and that forced Bmi1 expression had no obvious influence on ESC self-renewal. However, upon ESC differentiation Bmi1 effectively enhanced development of hematopoietic cells. Global transcriptional profiling identified a large array of genes that were differentially regulated during ESC differentiation by Bmi1. Importantly, we found that Bmi1 induced a prominent up-regulation of Gata2, a zinc finger transcription factor, which is essential for primitive hematopoietic cell generation from mesoderm. In addition, Bmi1 caused sustained growth and a more than 100-fold expansion of ESC-derived hematopoietic stem/progenitor cells within 2-3 weeks of culture. The enhanced proliferative capacity was associated with reduced Ink4a/Arf expression in Bmi1-transduced cells. Taken together, our experiments demonstrate distinct activities of Bmi1 in ESC and ESC-derived hematopoietic progenitor cells. In addition, Bmi1 enhances the propensity of ESC in differentiating towards the hematopoietic lineage. Thus, Bmi1 could be a candidate gene for engineered adult stem cell derivation from ESC. 8 samples in total. Bmi1 embryonic stem cells sample_1 (Bmi1_ESC_1) Bmi1 embryonic stem cells sample_2 (Bmi1_ESC_2) Untreated CCE embryonic stem cells (CCE_ESC_Control) Empty vector CCE embryonic stem cells (CCE_ESC_Vector) Bmi1 embryoid body sample_1 (Bmi1_EB_1) Bmi1 embryoid body sample_2 (Bmi1_EB_2) Empty vector control embryoid body sample_1 (Vector_EB_1) Empty vector control embryoid body sample_2 (Vector_EB_2)

Dataset Information

An anticlastogenic function for the Polycomb Group gene Bmi1.

Publications

An anticlastogenic function for the Polycomb Group gene Bmi1.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets