| Autor: |
Helmsauer, Konstantin, Valieva, Maria E., Ali, Salaheddine, Chamorro González, Rocío, Schöpflin, Robert, Röefzaad, Claudia, Bei, Yi, Dorado Garcia, Heathcliff, Rodriguez-Fos, Elias, Puiggròs, Montserrat, Kasack, Katharina, Haase, Kerstin, Keskeny, Csilla, Chen, Celine Y., Kuschel, Luis P., Euskirchen, Philipp, Heinrich, Verena, Robson, Michael I., Rosswog, Carolina, Toedling, Joern |
| Předmět: |
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| Zdroj: |
Nature Communications; 11/16/2020, Vol. 11 Issue 1, pN.PAG-N.PAG, 1p |
| Abstrakt: |
MYCN amplification drives one in six cases of neuroblastoma. The supernumerary gene copies are commonly found on highly rearranged, extrachromosomal circular DNA (ecDNA). The exact amplicon structure has not been described thus far and the functional relevance of its rearrangements is unknown. Here, we analyze the MYCN amplicon structure using short-read and Nanopore sequencing and its chromatin landscape using ChIP-seq, ATAC-seq and Hi-C. This reveals two distinct classes of amplicons which explain the regulatory requirements for MYCN overexpression. The first class always co-amplifies a proximal enhancer driven by the noradrenergic core regulatory circuit (CRC). The second class of MYCN amplicons is characterized by high structural complexity, lacks key local enhancers, and instead contains distal chromosomal fragments harboring CRC-driven enhancers. Thus, ectopic enhancer hijacking can compensate for the loss of local gene regulatory elements and explains a large component of the structural diversity observed in MYCN amplification. MYCN amplification is common in neuroblastomas. Here the authors analyse the MYCN amplicon structure and its epigenetic regulation by integrating short- and longread genomic and epigenomic data and find two classes of MYCN amplicons in neuroblastomas, one driven by local enhancers and the other by hijacking of distal regulatory elements. [ABSTRACT FROM AUTHOR] |
| Databáze: |
Complementary Index |
| Externí odkaz: |
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