6o5k

Structural highlights

Function

TIF1B_MOUSE Nuclear corepressor for KRAB domain-containing zinc finger proteins (KRAB-ZFPs). Mediates gene silencing by recruiting CHD3, a subunit of the nucleosome remodeling and deacetylation (NuRD) complex, and SETDB1 (which specifically methylates histone H3 at 'Lys-9' (H3K9me)) to the promoter regions of KRAB target genes. Enhances transcriptional repression by coordinating the increase in H3K9me, the decrease in histone H3 'Lys-9 and 'Lys-14' acetylation (H3K9ac and H3K14ac, respectively) and the disposition of HP1 proteins to silence gene expression. Recruitment of SETDB1 induces heterochromatinization. May play a role as a coactivator for CEBPB and NR3C1 in the transcriptional activation of ORM1. Also corepressor for ERBB4. Inhibits E2F1 activity by stimulating E2F1-HDAC1 complex formation and inhibiting E2F1 acetylation. May serve as a partial backup to prevent E2F1-mediated apoptosis in the absence of RB1. Important regulator of CDKN1A/p21(CIP1). Has E3 SUMO-protein ligase activity toward itself via its PHD-type zinc finger. Specifically sumoylates IRF7, thereby inhibiting its transactivation activity. Ubiquitinates p53/TP53 leading to its proteosomal degradation; the function is enhanced by MAGEC2 and MAGEA2, and possibly MAGEA3 and MAGEA6. Mediates the nuclear localization of KOX1, ZNF268 and ZNF300 transcription factors. Probably forms a corepressor complex required for activated KRAS-mediated promoter hypermethylation and transcriptional silencing of tumor suppressor genes (TSGs) or other tumor-related genes in colorectal cancer (CRC) cells. Required to maintain a transcriptionally repressive state of genes in undifferentiated embryonic stem cells (ESCs). In ESCs, in collaboration with SETDB1, is also required for H3K9me3 and silencing of endogenous and introduced retroviruses in a DNA-methylation independent-pathway (PubMed:20164836). Associates at promoter regions of tumor suppressor genes (TSGs) leading to their gene silencing. The SETDB1-TRIM28-ZNF274 complex may play a role in recruiting ATRX to the 3'-exons of zinc-finger coding genes with atypical chromatin signatures to establish or maintain/protect H3K9me3 at these transcriptionally active regions (By similarity). Acts as a corepressor for ZFP568 (PubMed:22110054, PubMed:27658112).[UniProtKB:Q13263]^{[1] [2] [3] [4] [5]}

See Also

• Ubiquitin protein ligase 3D structures

References

1. ↑ Matsui T, Leung D, Miyashita H, Maksakova IA, Miyachi H, Kimura H, Tachibana M, Lorincz MC, Shinkai Y. Proviral silencing in embryonic stem cells requires the histone methyltransferase ESET. Nature. 2010 Apr 8;464(7290):927-31. doi: 10.1038/nature08858. Epub 2010 Feb 17. PMID:20164836 doi:http://dx.doi.org/10.1038/nature08858
2. ↑ Okazaki IM, Okawa K, Kobayashi M, Yoshikawa K, Kawamoto S, Nagaoka H, Shinkura R, Kitawaki Y, Taniguchi H, Natsume T, Iemura S, Honjo T. Histone chaperone Spt6 is required for class switch recombination but not somatic hypermutation. Proc Natl Acad Sci U S A. 2011 May 10;108(19):7920-5. doi:, 10.1073/pnas.1104423108. Epub 2011 Apr 25. PMID:21518874 doi:http://dx.doi.org/10.1073/pnas.1104423108
3. ↑ Shibata M, Blauvelt KE, Liem KF Jr, Garcia-Garcia MJ. TRIM28 is required by the mouse KRAB domain protein ZFP568 to control convergent extension and morphogenesis of extra-embryonic tissues. Development. 2011 Dec;138(24):5333-43. doi: 10.1242/dev.072546. PMID:22110054 doi:http://dx.doi.org/10.1242/dev.072546
4. ↑ Murphy KE, Shylo NA, Alexander KA, Churchill AJ, Copperman C, Garcia-Garcia MJ. The Transcriptional Repressive Activity of KRAB Zinc Finger Proteins Does Not Correlate with Their Ability to Recruit TRIM28. PLoS One. 2016 Sep 22;11(9):e0163555. doi: 10.1371/journal.pone.0163555., eCollection 2016. PMID:27658112 doi:http://dx.doi.org/10.1371/journal.pone.0163555
5. ↑ Chang CJ, Chen YL, Lee SC. Coactivator TIF1beta interacts with transcription factor C/EBPbeta and glucocorticoid receptor to induce alpha1-acid glycoprotein gene expression. Mol Cell Biol. 1998 Oct;18(10):5880-7. PMID:9742105