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BCL6 is crucial for B-cell activation and lymphomagenesis. We used integrative genomics to explore BCL6 mechanism in normal and malignant B-cells. Surprisingly, BCL6 assembled distinct complexes at enhancers vs. promoters. At enhancers BCL6 preferentially recruited SMRT, which mediated H3K27 deacety...
ORGANISM(S): Homo sapiens 
To elucidate the mechanism of BCL6-mediated pre-B cell survival signaling, we investigated the gene expression pattern in BCR-ABL1-transformed BCL6+/+ and BCL6-/- B cell precursors. Pharmacological inhibition of BCR-ABL1 was performed with the BCR-ABL1 kinase inhibitor STI571 (Imatinib). BCR-ABL1 t...
ORGANISM(S): Mus musculus 
Our data demonstrated that Bcl6 directly binds and represses trafficking receptors S1pr1 and Grp183 by recruiting Hdac2 through the RD2 domain. Deregulation of these genes impairs B-cell migration and may contribute to the Germinal Center failure in Bcl6RD2MUT mice. RNAseq was performed in endogeno...
ORGANISM(S): Homo sapiens 
More than 50% of patients with chondrosarcomas exhibit gain-of-function mutations in either isocitrate dehydrogenase 1 (IDH1) or IDH2. In this study, we performed genome-wide CpG methylation sequencing of chondrosarcoma biopsies and found that IDH mutations were associated with DNA hypermethylation ...
ORGANISM(S): Homo sapiens 
Integrative epigenomic analysis identifies biomarkers and therapeutic targets in adult B-acute lymphoblastic leukemia. We performed DNA methylation (HELP array) and gene expression profiling in 215 samples of adult B-lineage acute lymphoblastic leukemia (ALL) and 12 normal preB samples. Adult B-lin...
ORGANISM(S): Homo sapiens 
The EZH2 histone methyltransferase is highly expressed in germinal center (GC) B-cells and targeted by somatic mutations in B-cell lymphomas. Here we find that EZH2 deletion or pharmacologic inhibition suppresses GC formation and functions in mice. EZH2 represses proliferation checkpoint genes and h...
ORGANISM(S): Homo sapiens 
AML1-ETO, a fusion protein generated by the t(8;21) translocation in acute myeloid leukemia, is a transcription factor implicated in both gene repression and activation. We now show that, in leukemic cells, AML1-ETO resides in and functions through a stable protein complex (AETFC) that contains seve...
ORGANISM(S): Homo sapiens 
Emerging evidence suggests that chromatin adopts a non-random three-dimensional (3D) topology and that the organization of genes into structural hubs and domains affects their transcriptional status. How chromatin conformation changes in diseases such as cancer is poorly understood. Moreover, how on...
ORGANISM(S): Homo sapiens 
This analysis focused on identifying factors that protect pre-B cells against DNA double strand break (DSB)-mediated DNA damage stress during pre-B cell differentiation. Differentiation of pre-B cells including immunoglobulin light chain gene recombination were performed by withdrawal of interleuki...
ORGANISM(S): Mus musculus 
Acute lymphoblastic leukemia (ALL), the commonest childhood malignancy, is characterized by recurring gross and submicroscopic structural genetic alterations that contribute to leukemogenesis. Disordered epigenetic regulation is a hallmark of many tumors, and while analysis of DNA methylation of lim...
ORGANISM(S): Homo sapiens 
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