Chromatin Regulator | Alias | |||||||||||||||||||||||||||||||||||||||
| RNF2 | RING1B;HIPI3;BAP1;DING;RING2;BAP-1 | |||||||||||||||||||||||||||||||||||||||
External Links: | Wiki GeneCards NCBI UniProt | |||||||||||||||||||||||||||||||||||||||
Related histone modifications: | H2Aub1 | |||||||||||||||||||||||||||||||||||||||
Introduction | ||||||||||||||||||||||||||||||||||||||||
| Full name: Ring Finger Protein 2. RNF2 is a component of polycomb repressive complex 1 (PRC1),is an E3 ubiquitin-protein ligase that catalyzes monoubiquitination of lys 119 of histone H2A (H2AK119ub),plays important roles in the regulation of Hox gene expression,X-chromosome inactivation,tumorigenesis and stem cell self-renewal(1-8).RNF2 interacts with Bmi-1 through extensive RING domain and its N-terminal tail to stabilize the interaction bwtween the E2 enzyme and the nucleosomal substrate to allow efficient ubiquitin transfer(8). | ||||||||||||||||||||||||||||||||||||||||
Function and Interaction | ||||||||||||||||||||||||||||||||||||||||
| RNF2 catalyzes monoubiquitination of lys 119 of histone H2A (H2AK119ub) and is a core component of polycomb repressive complex 1 (PRC1) which is required for transcriptional repression of various genes involved in development and cell proliferation(1-8).RNF2 interacts with AUTS2 in the presence of PCGF5 to form a PRC1.5-AUTS2 complex that activates transcription(5).RNF2 is able to catalyze monoubiquitination of H2AK119ub at the promoter of LTBP2,resulting in silencing of this negative regulator of TGFβ signaling and drives proliferation through direct transcriptional upregulation of the cell-cycle regulator CCND2 in melanoma(9). RNF2 also polyubiquitinates tumor suppressor TP53 in selective tumor types leading to tumor formation(10).RNF2 is an E3 ligase for K48-linked ubiquitination of AMBRA1,leading to downregulation of autophagy(11). | ||||||||||||||||||||||||||||||||||||||||
Disease Association | ||||||||||||||||||||||||||||||||||||||||
| Rnf2 regulates synapse maturation by modulating the insertion of functional AMPA receptors at the post-synaptic compartment(12). | ||||||||||||||||||||||||||||||||||||||||
ChIP-Seq data
ChIP-Seq data of related histone modifications
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| Notice: For bigwiggle or bed file download, if the browser cannot automatically download the file, users can right click the hyperlink and then click the "Save link as..." button, which will automatically redirect to download dialogue box, or click the "Copy link address" button and access the website in a new tab page. For data analysis in Cistrome, users should first login into the Cistrome website, then press the "Send Bed" or "Send Big wiggle" button. For data download by Cistrome, users can follow this tutorial. | ||||||||||||||||||||||||||||||||||||||||
References | ||||||||||||||||||||||||||||||||||||||||
| 1.Wang, H., Wang, L., Erdjument-Bromage, H., Vidal, M., Tempst, P., Jones, R.S., and Zhang, Y. (2004). Role of histone H2A ubiquitination in Polycomb silencing. Nature 431, 873-878. 2.Schoorlemmer, J., Marcos-Gutierrez, C., Were, F., Martinez, R., Garcia, E., Satijn, D.P., Otte, A.P., and Vidal, M. (1997). Ring1A is a transcriptional repressor that interacts with the Polycomb-M33 protein and is expressed at rhombomere boundaries in the mouse hindbrain. EMBO J 16, 5930-5942. 3.Bentley, M.L., Corn, J.E., Dong, K.C., Phung, Q., Cheung, T.K., and Cochran, A.G. (2011). Recognition of UbcH5c and the nucleosome by the Bmi1/Ring1b ubiquitin ligase complex. EMBO J 30, 3285-3297. 4.Cao, R., Tsukada, Y., and Zhang, Y. (2005). Role of Bmi-1 and Ring1A in H2A ubiquitylation and Hox gene silencing. Mol Cell 20, 845-854. 5.Gao, Z., Lee, P., Stafford, J.M., von Schimmelmann, M., Schaefer, A., and Reinberg, D. (2014). An AUTS2-Polycomb complex activates gene expression in the CNS. Nature 516, 349-354. 6.McGinty, R.K., Henrici, R.C., and Tan, S. (2014). Crystal structure of the PRC1 ubiquitylation module bound to the nucleosome. Nature 514, 591-596. 7.Taherbhoy, A.M., Huang, O.W., and Cochran, A.G. (2015). BMI1-RING1B is an autoinhibited RING E3 ubiquitin ligase. Nat Commun 6, 7621. 8.Li, Z., Cao, R., Wang, M., Myers, M.P., Zhang, Y., and Xu, R.M. (2006). Structure of a Bmi-1-Ring1B polycomb group ubiquitin ligase complex. J Biol Chem 281, 20643-20649. 9.Rai, K., Akdemir, K.C., Kwong, L.N., Fiziev, P., Wu, C.J., Keung, E.Z., Sharma, S., Samant, N.S., Williams, M., Axelrad, J.B., et al. (2015). Dual Roles of RNF2 in Melanoma Progression. Cancer Discov 5, 1314-1327. 10.Su, W.J., Fang, J.S., Cheng, F., Liu, C., Zhou, F., and Zhang, J. (2013). RNF2/Ring1b negatively regulates p53 expression in selective cancer cell types to promote tumor development. Proc Natl Acad Sci U S A 110, 1720-1725. 11.Xia, P., Wang, S., Huang, G., Du, Y., Zhu, P., Li, M., and Fan, Z. (2014). RNF2 is recruited by WASH to ubiquitinate AMBRA1 leading to downregulation of autophagy. Cell Res 24, 943-958. 12.Kumari, P., Srinivasan, B., and Banerjee, S. (2017). Modulation of hippocampal synapse maturation by activity-regulated E3 ligase via non-canonical pathway. Neuroscience 364, 226-241. | ||||||||||||||||||||||||||||||||||||||||
Figure Gallery
About Chromatin Regulator
Chromatin Regulator Cistrome
is a unique database integrating curated information of CRs, CR ChIP-seq datasets, CR related HM ChIP-seq datasets, and analysis of the relationship between CRs and HMs ChIP-seq pairs in human and mouse.