Breaching the Boundaries that Safeguard against Repression Vijay K. Tiwari, Stephen B. Baylin  Molecular Cell  Volume 34, Issue 4, Pages 395-397 (May 2009) DOI: 10.1016/j.molcel.2009.05.007 Copyright © 2009 Elsevier Inc. Terms and Conditions

Figure 1 A Model for How CTCF May Provide a Boundary to Prevent Tumor-Suppressor Gene Silencing (Top panel) Shown is CTCF-dependent tethering of upstream chromatin boundary elements to subnuclear structures, e.g., nucleolin, such that chromatin organization spatially separates upstream, inactive domains from active domain loops covering the TSS. Red lollipops indicate repressive histone marks; green lollipops indicate active histone modifications. The green arrow marks the TSS of the actively transcribed gene. (Middle panel) Loss of CTCF occupancy at the boundary element due to defective PARP-1-dependent CTCF PARlation leads to loss of interaction with subnuclear structures and of the higher-order organization into inactive and active domains. This leads to spreading of heterochromatin from the inactive upstream domain across the TSS, transcriptional silencing, and DNA hypermethylation of the tumor-suppressor gene. The red arrow marks the TSS of the silent gene. (Bottom panel) Treatment with drugs such as 5-AC leads to DNA demethylation in the promoter region, some gene re-expression, and acquisition of mixed active and repressive histone modifications. However, the boundary function is not restored. The dotted green arrow marks the TSS of the somewhat re-expressed gene. Molecular Cell 2009 34, 395-397DOI: (10.1016/j.molcel.2009.05.007) Copyright © 2009 Elsevier Inc. Terms and Conditions