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 | |
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 | |
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 | |
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] |