Disease relevance of SUZ12

• Upon removal of p16(INK4A) activity in primary human mammary epithelial cells, polycomb repressors, EZH2 and SUZ12, are up-regulated and recruited to HOXA9, a locus expressed during normal breast development and epigenetically silenced in breast cancer [1].
• Using oligonucleotide arrays, we first identified a cohort of genes whose expression changes upon siRNA-mediated removal of Suz12, a core component of PRC2/3, from colon cancer cells [2].
• Frequent fusion of the JAZF1 and JJAZ1 genes in endometrial stromal tumors [3].
• Analyses of tumor RNA indicate that a JAZF1/JJAZ1 fusion is present in all types of endometrial stromal tumors; however, the fusion appears to be rarer among endometrial stromal sarcomas that would be considered high-grade according to certain classification schemes [3].

High impact information on SUZ12

• We have mapped the Polycomb Repressive Complex 2 (PRC2) subunit SUZ12 across the entire nonrepeat portion of the genome in human embryonic stem (ES) cells [4].
• Importantly, recruitment of Suz12, Ezh2 and Eed to target promoters coincides with methylation of histone H3 on Lys 27 [2].
• We next identified additional putative Suz12 target genes by using ChIP coupled to CpG-island microarrays [2].
• Thus, our study establishes a critical role of SUZ12 in H3-lysine 27 methylation and Hox gene silencing [5].
• Chromatin immunoprecipitation (ChIP) assay identified a 500 bp region located 4 kb upstream of the HoxA9 transcription initiation site as a SUZ12 binding site, which responds to SUZ12 knockdown and might play an important role in regulating HoxA9 expression [5].

Biological context of SUZ12

• Using a stable SUZ12 knockdown cell line, we show SUZ12 knockdown results in cell growth defects, which correlate with genome-wide alteration on H3-K27 methylation as well as upregulation of a number of Hox genes [5].
• In conclusion, our data demonstrate an essential role of SUZ12 in regulating the activity of the PRC2/3 complexes, which are required for regulating proliferation and embryogenesis [6].
• We demonstrate that at this targeted locus, the up-regulation of polycomb repressors is accompanied by the recruitment of DNA methyltransferases and the hypermethylation of DNA, an endpoint, which we show to be dependent on SUZ12 expression [1].
• This type II deletion was found in 8 (38%) of 21 patients and is mediated by recombination between the JJAZ1 gene and its pseudogene [7].
• We have identified two zinc finger genes, which we have termed JAZF1 and JJAZ1, at the sites of the 7p15 and 17q21 breakpoints [3].

Anatomical context of SUZ12

• Most ESTs of classic histology showed evidence of JAZF1-JJAZ1 fusion (4 of 5 cases), whereas only one mixed smooth muscle ESN of 10 variant cases was positive [8].

Physical interactions of SUZ12

• Here, we show that SUZ12 interacts with WD-repeat protein MEP50 in vitro and in vivo [9].

Other interactions of SUZ12

• EZH2 is a component of the PRC2 histone methyltransferase complex, which also contains EED and SUZ12 and is required for the silencing of HOX gene expression during embryonic development [10].
• Association of Polycomb group SUZ12 with WD-repeat protein MEP50 that binds to histone H2A selectively in vitro [9].
• Prediction of the coding sequences of unidentified human genes. IV. The coding sequences of 40 new genes (KIAA0121-KIAA0160) deduced by analysis of cDNA clones from human cell line KG-1 [11].
• Mitotic recombination mediated by the JJAZF1 (KIAA0160) gene causing somatic mosaicism and a new type of constitutional NF1 microdeletion in two children of a mosaic female with only few manifestations [12].

Analytical, diagnostic and therapeutic context of SUZ12

• Using a nonnested reverse transcriptase-polymerase chain reaction approach, we assayed for JAZF1-JJAZ1 gene fusion transcripts in 10 cases with available fresh-frozen tissue [8].

References