TY - JOUR
T1 - Epigenomic landscape and 3D genome structure in pediatric high-grade glioma
AU - Wang, Juan
AU - Huang, Tina Yi Ting
AU - Hou, Ye
AU - Bartom, Elizabeth
AU - Lu, Xinyan
AU - Shilatifard, Ali
AU - Yue, Feng
AU - Saratsis, Amanda
N1 - Funding Information:
Acknowledgments: We would like to thank D. M. Scholtens and K. L. Bell Burdett for the assistance with statistical analyses. Funding: Research reported in this publication was supported by the NIH’s Natural Institute of Neurological Disease and Stroke, grant number
Publisher Copyright:
Copyright © 2021 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works. Distributed under a Creative Commons Attribution NonCommercial License 4.0 (CC BY-NC).
PY - 2021/6
Y1 - 2021/6
N2 - Pediatric high-grade gliomas (pHGGs), including glioblastoma multiforme (GBM) and diffuse intrinsic pontine glioma (DIPG), are morbid brain tumors. Even with treatment survival is poor, making pHGG the number one cause of cancer death in children. Up to 80% of DIPGs harbor a somatic missense mutation in genes encoding histone H3. To investigate whether H3K27M is associated with distinct chromatin structure that alters transcription regulation, we generated the first high-resolution Hi-C maps of pHGG cell lines and tumor tissue. By integrating transcriptome (RNA-seq), enhancer landscape (ChIP-seq), genome structure (Hi-C), and chromatin accessibility (ATAC-seq) datasets from H3K27M and wild-type specimens, we identified tumor-specific enhancers and regulatory networks for known oncogenes. We identified genomic structural variations that lead to potential enhancer hijacking and gene coamplification, including A2M, JAG2, and FLRT1. Together, our results imply three-dimensional genome alterations may play a critical role in the pHGG epigenetic landscape and contribute to tumorigenesis.
AB - Pediatric high-grade gliomas (pHGGs), including glioblastoma multiforme (GBM) and diffuse intrinsic pontine glioma (DIPG), are morbid brain tumors. Even with treatment survival is poor, making pHGG the number one cause of cancer death in children. Up to 80% of DIPGs harbor a somatic missense mutation in genes encoding histone H3. To investigate whether H3K27M is associated with distinct chromatin structure that alters transcription regulation, we generated the first high-resolution Hi-C maps of pHGG cell lines and tumor tissue. By integrating transcriptome (RNA-seq), enhancer landscape (ChIP-seq), genome structure (Hi-C), and chromatin accessibility (ATAC-seq) datasets from H3K27M and wild-type specimens, we identified tumor-specific enhancers and regulatory networks for known oncogenes. We identified genomic structural variations that lead to potential enhancer hijacking and gene coamplification, including A2M, JAG2, and FLRT1. Together, our results imply three-dimensional genome alterations may play a critical role in the pHGG epigenetic landscape and contribute to tumorigenesis.
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U2 - 10.1126/sciadv.abg4126
DO - 10.1126/sciadv.abg4126
M3 - Article
C2 - 34078608
AN - SCOPUS:85107269311
SN - 2375-2548
VL - 7
JO - Science Advances
JF - Science Advances
IS - 23
M1 - eabg4126
ER -
