Recent studies have solidified the role of the CTCF insulator protein in creating chromatin loops and boundaries that partition such domains 15. Such domains are evident in genome-wide contact maps generated by HiC 13, and have been termed ‘topologically-associated domains’ (TAD) or ‘contact domains’ 14-16. The human genome is organized into topological domains that represent discrete structural and regulatory units 12. IDH mutant gliomas thus manifest a CpG island methylator phenotype (G-CIMP) 10,11, though the functional significance of this altered epigenetic state remains unclear. TET enzymes catalyze a key step in the removal of DNA methylation 8,9. Mutant IDH protein produces a novel onco-metabolite, 2-hydroxyglutarate (2-HG), that interferes with iron-dependent hydroxylases, including the TET family of 5′-methylcytosine hydroxylases 3-7. Gain-of-function IDH mutations are initiating events that define major clinical and prognostic classes of gliomas 1,2. The present invention further relates to methods of altering chromatin topology by altering a boundary. In particular, the present invention relates to detection of mutations causing DNA hypermethylation phenotypes, CpG methylation within CTCF binding motifs, and aberrant gene expression caused by altered chromatin topology. The present invention relates generally to the diagnosis and treatment of diseases resulting from the alteration of chromatin boundaries between topologically-associated domains. The instant application contains a Sequence Listing which has been filed electronically in ASCII format and is hereby incorporated by reference in its entirety. The government has certain rights in the invention. HG006991 awarded by the National Institutes of Health. This invention was made with government support under Grant No. More specifically, all referenced documents are incorporated by reference to the same extent as if each individual document was specifically and individually indicated to be incorporated by reference. The foregoing application, and all documents cited therein or during their prosecution (“appln cited documents”) and all documents cited or referenced in the appln cited documents, and all documents cited or referenced herein (“herein cited documents”), and all documents cited or referenced in herein cited documents, together with any manufacturer's instructions, descriptions, product specifications, and product sheets for any products mentioned herein or in any document incorporated by reference herein, are hereby incorporated herein by reference, and may be employed in the practice of the invention. 22, 2017 as publication WO 2017/106290, which claims priority and benefit of U.S. 14, 2016 and published in English on Jun. § 371, of United States International Application Ser. RELATED APPLICATIONS AND INCORPORATION BY REFERENCE
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