A CTCF-Dependent Silencer Located in the Differentially Methylated Area May Regulate Expression of a Housekeeping Gene Overlapping a Tissue-Specific Gene Domain

Epigenetic Regulation of the Human Retinoblastoma Tumor Suppressor Gene Promoter by CTCF

“…2A; RbDCTCF+ 1Â+CTCFcDNA and RbDCTCF+2Â+CTCFcDNA). Notably, the FII sequence was unable to significantly contribute to the Rb promoter trans-activation, although it has been extensively shown that FII binds CTCF (15,16,22). These results suggest that CTCF requires a specific context within the human Rb promoter to perform its function; possibly along with cofactors interacting with CTCF and/or determining combinatorial use of zinc fingers by CTCF at this promoter.…”

“…DNA methylation analysis. Bisulfite analysis was done as previously described (15). The PCR primers for stable cell lines were designed against the plasmid sequences to avoid amplification of the endogenous promoter.…”

Epigenetic boundaries of tumour suppressor gene promoters: the CTCF connection and its role in carcinogenesis

“…One of the initial discoveries of such a role was the distribution of CTCF over the chicken, mouse and human β-globin loci, and more recently the chicken α-globin domain [54,[57][58][59]. The chicken β-globin group of genes is framed in vivo by binding of CTCF from a 16 kb region of condensed chromatin on the 5'-side and an olfactory receptor gene on the 3'-side [60].…”

“…Therefore, the list of aberrantly methylated CTCF DNA targets in different human cancers is not restricted to imprinted genes or the Igf2/H19 ICR sites (Fig. 4) [13,34,59]. This view has now been strengthened by observations from our laboratory (De La Rosa-Velázquez et al submitted), demonstrating that the CTCF-DNA interaction is methylation-sensitive and that the loss of CTCF from the Rb promoter correlates with the incorporation of a methyl-CpG-binding protein, with its cognate chromatin repressing components, which in turn could induce epigenetic silencing of this cell cycle regulator.…”

The inactivation of the π gene in chicken erythroblasts of adult lineage is not mediated by packaging of the embryonic part of the α-globin gene domain into a repressive heterochromatin-like structure

“…Even more importantly, in cultured erythroblasts of definite lineage, this segment demonstrated the same sensitivity to DNase I as the adult segment of the domain and the transcribed housekeeping gene GAPDH. One should also consider the distance between the α-globin domain and the upstream CpG island harboring the promoter of the C16orf35 gene 34 and the end of the embryonic segment of the α-globin domain. This distance constitutes only ~6 kb or ~30 nucleosomes.…”