High impact information on Trim28

• We show that its obligate corepressor, KAP1, can coordinate all the machinery required for stable gene silencing [1].
• Thus, KRIP-1 interacts with the KRAB-A region of C2H2 zinc finger proteins and may mediate or modulate KRAB-A transcriptional repressor activity [2].
• KRIP-1 is a member of the RBCC subfamily of the RING finger, or Cys3HisCys4, family of zinc binding proteins whose other members are known to play important roles in differentiation, oncogenesis, and signal transduction [2].
• We show that KAP1 is rapidly phosphorylated following DNA damage by members of the phosphatidylinositol-3 kinase-like family of kinases [3].
• Spatiotemporally controlled ablation of TIF1beta by using a germ cell lineage-specific CreER(T)/loxP system leads to testicular degeneration [4].

Biological context of Trim28

• Germ cell expression of the transcriptional co-repressor TIF1beta is required for the maintenance of spermatogenesis in the mouse [4].
• The gene for transcriptional intermediary factor 1beta (TIF1beta) encodes a transcriptional co-repressor known to play essential roles in chromatin remodeling as well as in early embryonic development [4].
• These results indicate that TIF1beta has important functions in the homeostasis of the seminiferous epithelium, and probably plays a crucial role in the network of paracrine interactions between germ cell subpopulations and/or Sertoli cells [4].
• During spermatogenesis, TIF1beta is preferentially associated with heterochromatin structures of Sertoli cells and round spermatids, as well as with meiotic chromosomes [4].
• This degeneration is not due to impairment of chromatin remodeling processes during meiosis and spermiogenesis, as TIF1beta-deficient spermatocytes are able to complete their differentiation into spermatozoa [4].

Anatomical context of Trim28

• TIF1beta protein was detected in wild-type but not TIF1beta(-/-) blastocysts [5].

Associations of Trim28 with chemical compounds

• Second, a specific inhibitor of histone deacetylases, trichostatin A, effectively redistributes KRAZ1 and KAP-1 from centromeric foci and partially relieves their silencing activities [6].

Physical interactions of Trim28

• Here we report that TIF1beta directly binds to the NRD and negatively regulates the c-Myb-dependent trans-activation [7].
• KAP-1 directly interacts with heterochromatin protein 1 (HP1), a dose-dependent regulator of heterochromatin-mediated silencing [6].

Other interactions of Trim28

• Furthermore, the Drosophila TIF1beta homolog, Bonus, negatively regulates Drosophila Myb activity [7].
• Oncogenic activation of c-Myb correlates with a loss of negative regulation by TIF1beta and Ski [7].
• These data strongly suggest that KRAB-ZFPs/KAP-1 silence transcription by dynamic recruitment of the target locus to the specific gene silencing compartment, centromeric heterochromatin, in a histone deacetylase-dependent manner [6].

References