Figure 7: Genetic interaction between Tctp and PBAP and a model for nuclear Tctp function for genome stability.

(a) The schematic drawing of Brm chromatin remodelling complexes. Brm-containing chromatin remodelers can be divided into two types: BAP and PBAP according to their specific subunits, OSA and Bap160/170/SAYP, respectively. Based on genetic interactions (Fig. 6), Tctp seems to preferentially interact with PBAP than BAP. (b) A schematic model of novel nuclear Tctp functions for the stability of repeated sequences (rDNA and pericentromeric heterochromatin). Note that rDNA locus is not a part of heterochromatin although it is proximal to or surrounded by pericentromeric heterochromatin. Tctp keeps the stability of repeated sequences through three possible mechanisms: (Step 1) Tctp inhibits excess Brm activity, thereby regulating proper transcription level of various genes including transposons and stabilizing pericentromeric heterochromatin. caRNA expression and Pol-I activity regulated by Brm may also affect stability of pericentromeric heterochromatin (Step 1a and 1b, respectively). Brm may regulate the chromatin boundary (Step 1c). It might also be possible that Tctp mutations affect PEV by elevating the Brm activity within the regions of pericentromeric heterochromatin (Step 1d). (Step 2) Tctp positively regulates su(var)3-9 transcription by direct binding to su(var)3-9 locus, facilitating H3K9 methylation in pericentromeric regions. (Step 3) Brm or Pol-I may also be suppressed by the interaction between Tctp and ATM. See Discussion for details.