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HoxBlinc lncRNA reprograms CTCF-independent TADs to drive leukemic transcription and HSC dysregulation in NUP98 fusion transformed leukemia

ABSTRACT: This SuperSeries is composed of the SubSeries listed below.

ORGANISM(S): Mus musculus Homo sapiens

PROVIDER: GSE269258 | GEO | 2025/01/31

REPOSITORIES: GEO

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Hoxblinc lncRNA reprograms CTCF-independent TADs to drive leukemic transcription and HSC dysregulation in NUP98 fusion transformed leukemia [CTCF-HiChIP-seq]

Project description:We found NUP98 fusions activate Hoxb-associated lncRNA, HoxBlinc that occupies homeotic/oncogenic topologically associated domain (TAD) boundaries in malignant hematopoiesis. Aberration of HoxBlinc led to recruitment of MLL1 complex and reorganization of homeotic/oncogenicTADs that enhanced chromatin accessibilities and aberrantly activated homeotic/hematopoietic oncogenes defined by Hoxblinc chromatin occupancies in NUP98-PHF23 related murine leukemia cells. Eliminated HoxBlinc in NUP98 fusion-driven leukemic cells resulted in loss of Hoxblinc binding, TAD integrity, recruitment of MLL complex, and MLL driven H3K4me3 and chromatin accessibility within the HoxBlinc defined domain in a CTCF independent manner, leading to inhibiting homeotic/leukemic oncogenes and mitigating NUP98 fusion-driven leukemia in xenografted mouse models. Moreover, overexpression of HoxBlinc in mouse bone marrow hematopoietic compartment developed multiple leukemia resembling NUP98-PHF23 knock-in mice via enhancing HoxBlinc binding and TAD formation to transcriptionally expanding HS/PC and myeloid/lymphoid subpopulations leading to leukemogenesis. Our studies reveal a CTCF independent role of HoxBlinc in leukemic TAD organization and oncogenic gene regulatory networks in NUP98-fusion related leukemia.

2025-01-31 | GSE283303 | GEO

Hoxblinc lncRNA reprograms CTCF-independent TADs to drive leukemic transcription and HSC dysregulation in NUP98 fusion transformed leukemia [RNA-Seq]

Project description:We found NUP98 fusions activate Hoxb-associated lncRNA, HoxBlinc that occupies and regulates homeotic/oncogenic topologically associated domain (TAD) in malignant hematopoiesis. Aberration of HoxBlinc led to recruitment of MLL1 complex , altered chromatin landscape (both H3K4me3 and chromatin accessibility), and HOX/homeotic gene activatiion in NUP98-PHF23 fusion driven leukemia and HoxBlinc -Tg models. Conversely, eliminated HoxBlinc in NUP98 fusion-driven leukemic cells resulted in loss of Hoxblinc binding, TAD integrity, recruitment of MLL complex, and MLL driven H3K4me3 and chromatin accessibility within the HoxBlinc defined domain in a CTCF independent manner, leading to inhibiting homeotic/leukemic oncogenes and mitigating NUP98 fusion-driven leukemia in xenografted mouse models. Thus, our studies revealed a CTCF independent role of HoxBlinc in leukemic TAD organization and oncogenic gene regulatory networks in NUP98-fusion related leukemia.

2025-01-31 | GSE269226 | GEO

Hoxblinc lncRNA reprograms CTCF-independent TADs to drive leukemic transcription and HSC dysregulation in NUP98 fusion transformed leukemia [ChIRP-seq]

2025-01-31 | GSE269224 | GEO

Hoxblinc lncRNA reprograms CTCF-independent TADs to drive leukemic transcription and HSC dysregulation in NUP98 fusion transformed leukemia [scRNA-Seq]

2025-01-31 | GSE269219 | GEO

Hoxblinc lncRNA reprograms CTCF-independent TADs to drive leukemic transcription and HSC dysregulation in NUP98 fusion transformed leukemia [Hi-C]

2025-01-31 | GSE269218 | GEO

Hoxblinc lncRNA reprograms CTCF-independent TADs to drive leukemic transcription and HSC dysregulation in NUP98 fusion transformed leukemia [ChIP-Seq]

2025-01-31 | GSE269217 | GEO

Hoxblinc lncRNA reprograms CTCF-independent TADs to drive leukemic transcription and HSC dysregulation in NUP98 fusion transformed leukemia [ATAC-Seq]

2025-01-31 | GSE269216 | GEO

Hoxblinc lncRNA reprograms CTCF-independent TADs to drive leukemic transcription and HSC dysregulation in NUP98 fusion transformed leukemia [CUT&Run]

2025-01-31 | GSE269221 | GEO

HoxBlinc lncRNA reprograms CTCF-independent TADs to drive leukemic transcription and HSC dysregulation in NUP98 fusion transformed leukemia

Project description:HoxBlinc lncRNA reprograms CTCF-independent TADs to drive leukemic transcription and HSC dysregulation in NUP98 fusion transformed leukemia

| PRJNA1120835 | ENA

Hoxblinc lncRNA reprograms CTCF-independent TADs to drive leukemic transcription and HSC dysregulation in NUP98 fusion transformed leukemia [CTCF-HiChIP-seq]

Project description:Hoxblinc lncRNA reprograms CTCF-independent TADs to drive leukemic transcription and HSC dysregulation in NUP98 fusion transformed leukemia [CTCF-HiChIP-seq]

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