Earlier results had revealed PRC1
regulates gene expression in stem cells, but not the specifics how and when.
ANRIL has been postulated to be a scaffold for the PRC1
and PRC2 (35).
In proliferating cells, the SAFA and PANDA interaction recruits Polycomb repressive complex 1 (PRC1
) and PRC2 complexes to senescence target genes including CDKN1A in order to silence their expression .
Sudbery et al., "KDM2B links the polycomb repressive complex 1 (PRC1
) to recognition of CpG islands," eLife, vol.
This trend is also present for the case of rs8042680 (PRC1
), which has much higher risk allele frequency in the Mongolian sample compared to the Caucasians (0.92 versus 0.72; [F.sub.ST] = 0.67).
Batsche et al., "The PRC1
polycomb group complex interacts with PLZF/RARA to mediate leukemic transformation," Genes and Development, vol.
While many loci appear to contribute broadly to T2D risk, some loci have currently been confirmed in European populations only, including WFS1, NOTCH2, THADA, ADAMTS9, TSPAN8/LGR5, INSIGF2, ADCY5, GCK, MTRNR1B, HMGA2, HNF1A, ZBED3, KLF14, ZFAND6, PRC1
, TLES/CHCHD9, and RBMS1 [109, 116, 153-155].
Other enzymatic effectors of the epigenetic machinery include histone deacetylases (HDACs) and polycomb repressor complexes (PRC1
Although histone H2A mono-ubiquitylation in plants was initially questioned, recent studies in Arabidopsis revealed the presence of plant homologues to PRC1
components, the Polycomb complex that mediates H2A mono-ubiquitylation in animals, indicating the existence of PRC1-like complexes in plants.
(4) One such enzyme called EZH2 has intrinsic histone H3K27 methyl transferase activity; it assembles into a multiprotein complex called polycomb repressive complex 2 (PRC2) that, together with another protein complex (i.e., PRC1
), maintains a state of transcriptional repression and plays an important role in gene silencing (Muntean and Hess 2009).
Other genetic loci associated with type 2 diabetes are ZBED3 (Zinc finger, BED type containing), TP53INP1 (Tumor protein p53 nuclear protein also known as stress inducible protein), CHCHD9 (Coiled-coil-helix-coiled coil-helix domain containing 9), CENTD2 (Arf-GAP with Rho-GAP domain, ANK repeat and PH domain containing protein 1), KCNQ1 (Potassium voltage gated channel subfamily KQT member 1), HMGA2 (High mobility group AT hook 2), HNF1A (Hepatocyte nuclear factor 1 home box A), PRC1
(Protein regulator of cytokinesis 1), ZFAND6 (Zinc finger, AN-1 type domain), DUSP9 (Dual specificity phosphatase 9).
Fourteen loci reached genome wide significance: 2 previously identified genes, [melatonin receptor 1B (MTNR1B) and IRS1] and 12 novel loci [B-cell CLL/lymphoma 11A (zinc finger protein) (BCL11A); zinc finger, BED-type containing 3 (ZBED3); Kruppel-like factor 14 (KLF14); tumor protein p53 inducible nuclear protein 1 (TP53INP1); transducin-like enhancer of split 4 (TLE4); coiled-coil-helix-coiled-coil-helix domain containing 9 (CHCHD9); KCNQ1; ArfGAP with RhoGAP domain, ankyrin repeat and PH domain 1(ARAP1); high mobility group AT-hook 2 (HMGA2); HNF1A; zinc finger, AN1-type domain 6 (ZFAND6); protein regulator of cytokinesis 1 (PRC1
); and dual specificity phosphatase 9 (D17SP9)] (Table 1).