Choudhary, R. | bioRxiv Science

bioRxiv2021

Biop-C: A Method for Chromatin Interactome Analysis of Solid Cancer Needle Biopsy Samples

A major challenge in understanding the 3D genome organization of cancer samples is the lack of a method adapted to solid cancer needle biopsy samples. Here we developed Biop-C, a modified in situ Hi-C method, and applied it to characterize three nasopharyngeal cancer patient samples. We identified Topologically-Associated Domains (TADs), chromatin interaction loops, and Frequently Interacting regions (FIREs) at key oncogenes in nasopharyngeal cancer from Biop-C heat maps. Our results demonstrate the utility of our Biop-C method in investigating the 3D genome organization in solid cancers, and the importance of 3D genome organization in regulating oncogenes in nasopharyngeal cancer.

genomics↗

bioRxiv2020

Three-dimensional Genome Organization Maps in Normal Haematopoietic Stem Cells and Acute Myeloid Leukemia

Acute Myeloid Leukemia (AML) is a highly lethal blood cancer arising due to aberrant differentiation of haematopoietic stem cells. Here we obtained 3D genome organization maps by Hi-C in the CD34+ haematopoietic stem cells from three healthy individuals and eight individuals with AML, and found that AML have increased loops to oncogenes compared with normal CD34+ cells. The MEIS1 oncogenic transcription factor is regulated by a Frequently Interacting Region (FIRE). This FIRE is only present in normal bone marrow samples, and four of eight AML sample. FIRE presence is associated with MEIS1 expression. CRISPR excision of a FIRE boundary led to loss of MEIS1 and reduced cell growth. Moreover, MEIS1 can bind to the promoter of HOXA9, and HOXA9 shows gain of Acute Myeloid Leukemia-specific super-enhancers that loop to the HOXA9 promoter. SignificanceWe found that Acute Myeloid Leukemias have more chromatin loops to oncogenes compared with normal blood stem cells. We identified heterogeneity in chromatin interactions at oncogenes, and heterogeneity in super-enhancers that loop to oncogenes, as two key epigenetic mechanisms that underlie MEIS1 and HOXA9 oncogene expression respectively.

cancer biology↗