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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