A Unique B-cell Regulome links Notch to Downstream Oncogenic Pathways in Small B-cell Lymphoma
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE97541 | GEO | 2018/06/03
REPOSITORIES: GEO
Similar Datasets
Project description:Gain-of-function Notch mutations are recurrent in mature small B cell lymphomas such as mantle cell lymphoma (MCL) and chronic lymphocytic leukemia (CLL), but the Notch target genes that contribute to B cell oncogenesis are largely unknown. We performed integrative analysis of Notch-regulated transcripts, genomic binding of Notch transcription complexes, and genome conformation data to identify direct Notch target genes in MCL cell lines. This B cell Notch regulome is largely controlled through Notch-bound distal enhancers and includes genes involved in B cell receptor and cytokine signaling and the oncogene MYC, which sustains proliferation of Notch-dependent MCL cell lines via a Notch-regulated lineage-restricted enhancer complex. Expression of direct Notch target genes is associated with Notch activity in an MCL xenograft model and in CLL lymph node biopsies. Our findings provide key insights into the role of Notch in MCL and other B cell malignancies and have important implications for therapeutic targeting of Notch-dependent oncogenic pathways.
| S-EPMC5687286 | biostudies-literature
Project description:Purpose: To investigate the impact of oncogenic Notch on the 3D genome organization of cancer cells. Methods: We generated cohesin HiChIP and 1D epigenomic data sets in two different Notch-dependent cancer cell types, triple-negative breast cancer (TNBC) and mantle cell lymphoma (MCL), in the Notch-on and -off states. Results: We report here that Notch transcription complexes control their direct target genes through two distinct regulatory modes: either through existing loops or by facilitating new long-range regulatory interactions. This combination of pre-existing and Notch-promoted loops coalesce enhancers and promoters to form highly interacting clusters, termed “3D cliques”. Notch preferentially activates enhancers and promotes looping interactions within highly connected 3D cliques that regulate key oncogenes. Conclusions: These observations suggest a general mechanism that oncogenic transcription factors can exploit to regulate the transcriptional outputs of cancer cells.
2019-02-27 | GSE116872 | GEO
Project description:Purpose: To investigate the impact of oncogenic Notch on the 3D genome organization of cancer cells. Methods: We generated cohesin HiChIP and 1D epigenomic data sets in two different Notch-dependent cancer cell types, triple-negative breast cancer (TNBC) and mantle cell lymphoma (MCL), in the Notch-on and -off states. Results: We report here that Notch transcription complexes control their direct target genes through two distinct regulatory modes: either through existing loops or by facilitating new long-range regulatory interactions. This combination of pre-existing and Notch-promoted loops coalesce enhancers and promoters to form highly interacting clusters, termed “3D cliques”. Notch preferentially activates enhancers and promotes looping interactions within highly connected 3D cliques that regulate key oncogenes. Conclusions: These observations suggest a general mechanism that oncogenic transcription factors can exploit to regulate the transcriptional outputs of cancer cells.
2019-02-27 | GSE116869 | GEO
Project description:Purpose: To investigate the impact of oncogenic Notch on the 3D genome organization of cancer cells. Methods: We generated cohesin HiChIP and 1D epigenomic data sets in two different Notch-dependent cancer cell types, triple-negative breast cancer (TNBC) and mantle cell lymphoma (MCL), in the Notch-on and -off states. Results: We report here that Notch transcription complexes control their direct target genes through two distinct regulatory modes: either through existing loops or by facilitating new long-range regulatory interactions. This combination of pre-existing and Notch-promoted loops coalesce enhancers and promoters to form highly interacting clusters, termed “3D cliques”. Notch preferentially activates enhancers and promotes looping interactions within highly connected 3D cliques that regulate key oncogenes. Conclusions: These observations suggest a general mechanism that oncogenic transcription factors can exploit to regulate the transcriptional outputs of cancer cells.
2019-02-27 | GSE116867 | GEO
Project description:Purpose: To investigate the impact of oncogenic Notch on the 3D genome organization of cancer cells. Methods: We generated cohesin HiChIP and 1D epigenomic data sets in two different Notch-dependent cancer cell types, triple-negative breast cancer (TNBC) and mantle cell lymphoma (MCL), in the Notch-on and -off states. Results: We report here that Notch transcription complexes control their direct target genes through two distinct regulatory modes: either through existing loops or by facilitating new long-range regulatory interactions. This combination of pre-existing and Notch-promoted loops coalesce enhancers and promoters to form highly interacting clusters, termed “3D cliques”. Notch preferentially activates enhancers and promotes looping interactions within highly connected 3D cliques that regulate key oncogenes. Conclusions: These observations suggest a general mechanism that oncogenic transcription factors can exploit to regulate the transcriptional outputs of cancer cells.
2019-02-27 | GSE116871 | GEO
Project description:Purpose: To investigate the impact of oncogenic Notch on the 3D genome organization of cancer cells. Methods: We generated cohesin HiChIP and 1D epigenomic data sets in two different Notch-dependent cancer cell types, triple-negative breast cancer (TNBC) and mantle cell lymphoma (MCL), in the Notch-on and -off states. Results: We report here that Notch transcription complexes control their direct target genes through two distinct regulatory modes: either through existing loops or by facilitating new long-range regulatory interactions. This combination of pre-existing and Notch-promoted loops coalesce enhancers and promoters to form highly interacting clusters, termed “3D cliques”. Notch preferentially activates enhancers and promotes looping interactions within highly connected 3D cliques that regulate key oncogenes. Conclusions: These observations suggest a general mechanism that oncogenic transcription factors can exploit to regulate the transcriptional outputs of cancer cells.
2019-02-27 | GSE116870 | GEO
Project description:Purpose: To investigate the impact of oncogenic Notch on the 3D genome organization of cancer cells. Methods: We generated cohesin HiChIP and 1D epigenomic data sets in two different Notch-dependent cancer cell types, triple-negative breast cancer (TNBC) and mantle cell lymphoma (MCL), in the Notch-on and -off states. Results: We report here that Notch transcription complexes control their direct target genes through two distinct regulatory modes: either through existing loops or by facilitating new long-range regulatory interactions. This combination of pre-existing and Notch-promoted loops coalesce enhancers and promoters to form highly interacting clusters, termed “3D cliques”. Notch preferentially activates enhancers and promotes looping interactions within highly connected 3D cliques that regulate key oncogenes. Conclusions: These observations suggest a general mechanism that oncogenic transcription factors can exploit to regulate the transcriptional outputs of cancer cells.
2019-02-27 | GSE116868 | GEO
Project description:Purpose: To investigate the impact of oncogenic Notch on the 3D genome organization of cancer cells. Methods: We generated cohesin HiChIP and 1D epigenomic data sets in two different Notch-dependent cancer cell types, triple-negative breast cancer (TNBC) and mantle cell lymphoma (MCL), in the Notch-on and -off states. Results: We report here that Notch transcription complexes control their direct target genes through two distinct regulatory modes: either through existing loops or by facilitating new long-range regulatory interactions. This combination of pre-existing and Notch-promoted loops coalesce enhancers and promoters to form highly interacting clusters, termed “3D cliques”. Notch preferentially activates enhancers and promotes looping interactions within highly connected 3D cliques that regulate key oncogenes. Conclusions: These observations suggest a general mechanism that oncogenic transcription factors can exploit to regulate the transcriptional outputs of cancer cells.
2019-02-27 | GSE116875 | GEO
Project description:Purpose: To investigate the impact of oncogenic Notch on the 3D genome organization of cancer cells. Methods: We generated cohesin HiChIP and 1D epigenomic data sets in two different Notch-dependent cancer cell types, triple-negative breast cancer (TNBC) and mantle cell lymphoma (MCL), in the Notch-on and -off states. Results: We report here that Notch transcription complexes control their direct target genes through two distinct regulatory modes: either through existing loops or by facilitating new long-range regulatory interactions. This combination of pre-existing and Notch-promoted loops coalesce enhancers and promoters to form highly interacting clusters, termed “3D cliques”. Notch preferentially activates enhancers and promotes looping interactions within highly connected 3D cliques that regulate key oncogenes. Conclusions: These observations suggest a general mechanism that oncogenic transcription factors can exploit to regulate the transcriptional outputs of cancer cells.
2019-02-27 | GSE116874 | GEO
Project description:Purpose: To investigate the impact of oncogenic Notch on the 3D genome organization of cancer cells. Methods: We generated cohesin HiChIP and 1D epigenomic data sets in two different Notch-dependent cancer cell types, triple-negative breast cancer (TNBC) and mantle cell lymphoma (MCL), in the Notch-on and -off states. Results: We report here that Notch transcription complexes control their direct target genes through two distinct regulatory modes: either through existing loops or by facilitating new long-range regulatory interactions. This combination of pre-existing and Notch-promoted loops coalesce enhancers and promoters to form highly interacting clusters, termed “3D cliques”. Notch preferentially activates enhancers and promotes looping interactions within highly connected 3D cliques that regulate key oncogenes. Conclusions: These observations suggest a general mechanism that oncogenic transcription factors can exploit to regulate the transcriptional outputs of cancer cells.
2019-02-27 | GSE116873 | GEO