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Table 3 Architectural changes and disease

From: Three-dimensional genome architecture and emerging technologies: looping in disease

Architectural component Disease phenotype or mutation effect Underlying cause or architectural change References
CTCF Silencing of tumor suppressor XAF1 Hypermethylation of CTCF-binding site near XAF1 promoter [119]
CTCF Illegitimate enhancer access of PDGFRA and its overexpression Hypermethylation of CTCF-binding site due to IDH mutation and disruption of TAD boundary [120]
CTCF Human limb malformation Altered TAD structure surrounding WNT6/IHH/EPHA4/PAX3 due to deletion, duplication or inversion in CTCF boundary element [53]
CTCF-cohesin Activation of proto-oncogenes in T-cell acute lymphoblastic leukemia Microdeletion of insulated boundary and aberrant access of enhancer to oncogene [54]
Cohesin loading factor NIPBL in 50% of cases Cornelia de Lange syndrome NIPBL mutation leads to chromatin decompaction in gene-rich regions. Chromatin architectural dysregulation suspected, but no direct evidence [19, 121]
MED12 X-linked mental retardation Opitz Kaveggia syndrome Recurrent mutation R961W in MED12, which affects its interaction with ncRNA a-1 and ncRNA a-3, and, therefore, likely disruption of regulatory loops mediated by MED12 and ncRNAs [122, 123]
Lamin A Hutchinson–Gilford Progeria syndrome Point mutation in lamin A, loss of H3K27me3, which in turn leads to global loss of spatial chromatin structure at the nuclear lamina [124,125,126]
Long non-coding RNA (lncRNA) CCAT1-L Colorectal cancer This lncRNA is transcribed from an 8q24 gene desert and interacts with CTCF to form looping structuresat the MYC locus, leading to overexpression [127]
lncRNA CISR-ACT Brachydactyly type E Translocation-mediated disruption of cis-interactions between a lncRNA and the parathyroid hormone-like hormone (PTHLH) gene, reducing its expression level [128]
  1. lncRNA long non-coding RNA, ncRNA non-coding RNA