Hi-C detects novel structural variants in HL-60 and HL-60/S4 cell lines

Jacobson, Elsie C.; Grand, Ralph S.; Perry, Jo K.; Vickers, Mark H.; Olins, Ada L.; Olins, Donald E.; O’Sullivan, Justin M.

doi:10.1101/482208

Cited by 2 publications

(1 citation statement)

References 64 publications

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“…2018 [36]. Hi-C and RNA-seq were used to identify translocations and other structural variants specific to HL-60/S4 [73]. Cells from the same seed-lot were used in all studies.…”

Section: Cell Culturementioning

confidence: 99%

TNF-α differentially regulates cell cycle genes in promyelocytic and granulocytic HL-60/S4 cells

Jacobson

Perry

Vickers

et al. 2018

Preprint

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Tumor necrosis factor alpha (TNF-α) is a potent cytokine involved in systemic inflammation and immune modulation. Signaling responses that involve TNF-α are context dependent and capable of stimulating pathways promoting both cell death and survival. TNF-α treatment has been investigated as part of a combined therapy for acute myeloid leukemia due to its modifying effects on all-trans retinoic acid (ATRA) mediated differentiation into granulocytes.To investigate the interaction between cellular differentiation and TNF-α, we performed RNA-sequencing on two forms of the human HL-60/S4 promyelocytic leukemia cell line treated with TNF-α. The ATRA-differentiated granulocytic form of HL-60/S4 cells had an enhanced transcriptional response to TNF-α treatment compared to the undifferentiated promyelocytes. The observed TNF-α responses included differential expression of cell cycle gene sets, which were generally upregulated in TNF-α treated promyelocytes, and downregulated in TNF-α treated granulocytes. This is consistent with TNF-α induced cell cycle repression in granulocytes and cell cycle progression in promyelocytes. Moreover, comparisons with gene expression changes associated with differentiation indicated that TNF-α treatment of granulocytes shifts the transcriptome towards that of a macrophage.We conclude that TNF-α treatment promotes a divergent transcriptional program in promyelocytes and granulocytes. TNF-α promotes cell cycle associated gene expression in promyelocytes. In contrast, TNF-α stimulated granulocytes have reduced cell cycle gene expression, and a macrophage-like transcriptional program.

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“…2018 [36]. Hi-C and RNA-seq were used to identify translocations and other structural variants specific to HL-60/S4 [73]. Cells from the same seed-lot were used in all studies.…”

Section: Cell Culturementioning

confidence: 99%

TNF-α differentially regulates cell cycle genes in promyelocytic and granulocytic HL-60/S4 cells

Jacobson

Perry

Vickers

et al. 2018

Preprint

Self Cite

View full text Add to dashboard Cite

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Somatic structural variant formation is guided by and influences genome architecture

Sidiropoulos

Mardin

Rodríguez-González

et al. 2021

Preprint

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The occurrence and formation of genomic structural variants (SV) is known to be influenced by the 3D chromatin architecture , but the extent and magnitude has been challenging to study. Here, we apply Hi-C to study chromatin organization before and after induction of chromothripsis in human cells. We use Hi-C to manually assemble the derivative chromosomes following the massive complex rearrangements, which allowed us to study the sources of SV formation and their consequences on gene regulation. We observe an action-reaction interplay whereby the 3D chromatin architecture directly impacts on the location and formation of SVs. In turn, the SVs reshape the chromatin organization to alter the local topologies, replication timing and gene regulation in cis. We show that genomic compartments and replication timing are important determinants for juxtaposing distant loci to form SVs across 30 different cancer types with a pronounced abundance of SVs between early replicating regions in uterine cancer. We find that SVs frequently occur at 3D loop-anchors, cause compartment switching and changes in replication timing, and that this is a major source of SV-mediated effects on nearby gene expression changes.

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Hi-C detects novel structural variants in HL-60 and HL-60/S4 cell lines

Cited by 2 publications

References 64 publications

TNF-α differentially regulates cell cycle genes in promyelocytic and granulocytic HL-60/S4 cells

TNF-α differentially regulates cell cycle genes in promyelocytic and granulocytic HL-60/S4 cells

Somatic structural variant formation is guided by and influences genome architecture

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