CTCF is a uniquely versatile transcription regulator linked to epigenetics and disease

High‐resolution analysis of 16q22.1 in breast carcinoma using DNA amplifiable probes (multiplex amplifiable probe hybridization technique) and immunohistochemistry

“…The tumour suppressor role of CTCF in cancer is suspected because of its involvement in regulating the expression of some genes that are directly implicated in cancer (i.e., MYC, IGF2, p53, P27, p19/ARF and BRCA1) [45][46][47] and its cell growth inhibitory effect. In addition, some tumour specific mutations within the zinc finger domain have previously been detected in some tumours, including breast cancer 48,49 and a tumour-suppressor role of E2F-4 has previously been suggested in breast cancer. 29 A major role for E2F-4 in cancer is suggested because of its key role in the control of cell cycle, cell growth and apoptosis, its association with p130, p107 and pRb and its abundance in noncycling cells.…”

Heterochromatin?many flavours, common themes

“…Firstly, there are a small number of cases that demonstrate that methylation of a DNA sequence can directly interfere with interactions of that sequence with transacting factors and initiate silencing directly. (56,57) In addition, MeCP2 was shown to tether histone methylation activity to a methylated transgene (55) and methylation of imprinting centres can trigger heterochromatin formation. (8,48) Our knowledge of the mechanisms behind this is sketchy, but we do know that some proteins can bind specifically to unmethylated imprinting centres to prevent subsequent CpG methylation.…”

“…(8,48) Our knowledge of the mechanisms behind this is sketchy, but we do know that some proteins can bind specifically to unmethylated imprinting centres to prevent subsequent CpG methylation. (56) In cancer, de novo CpG methylation accompanies gene silencing and precedes histone methylation. (58) But how do DNMTs methylate specific CpG islands if they are not sequence-specific?…”

“…The methylation of some imprinting centres is associated with activity of the associated imprinted gene, which can be explained by a mechanism whereby methylation displaces trans-acting factors associated with repression. (56) Pathways to heterochromatin Though similar factors are involved in heterochromatin formation at different loci, there is no single pathway to heterochromatin formation (Figs. 2 and 3).…”

Targeted regulation of imprinted genes by synthetic zinc-finger transcription factors

“…Primary to this phenomenon is the imprinting control region located in the 5 0 -flank of H19, which prevents the enhancers located 3 0 to the H19 gene from interacting with the IGF2 promoters some 80 kb away on the maternal chromosome, while silencing the H19 gene on the paternal chromosome. 37 Mechanistically, these processes remain poorly understood although the repression of the maternally derived IGF2 may involve the chromatin insulator protein CTCF, 38 which interacts with the H19 ICR in an allele-specific 39 and methylation-sensitive manner. [39][40][41] The fact that a ZFP transcription factor can bind to the IGF2 promoter and activate expression of the transcriptionally silent allele of IGF2 rules out models for insulator function in which the IGF2 promoter region is held within a repressive chromatin architecture, or is compartmentalized into a region or zone of the nucleus recalcitrant to the process of transcription.…”