9k22

A novel histone H3K27 reader, CBFA2T2, inhibits H3K27me3 demethylation and tumor growth by regulating metabolic genes and metabolite levels

Structural highlights

9k22 is a 2 chain structure with sequence from Mus musculus. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	X-ray diffraction, Resolution 2.81Å
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Disease

MTG8R_MOUSE Required for tumorigenesis in a AOM/DSS colitis-associated carcinoma model. May be involved in intestinal tumorigenesis.^[1]

Function

MTG8R_MOUSE Transcriptional corepressor which facilitates transcriptional repression via its association with DNA-binding transcription factors and recruitment of other corepressors and histone-modifying enzymes. Via association with PRDM14 is involved in regulation of embryonic stem cell (ESC) pluripotency. Involved in primordial germ cell (PCG) formation (PubMed:27281218). Stabilizes PRDM14 and OCT4 on chromatin in a homooligomerization-dependent mannerCan repress the expression of MMP7 in a ZBTB33-dependent manner (By similarity). Through heteromerization with CBFA2T3/MTG16 may be involved in regulation of the proliferation and the differentiation of erythroid progenitors by repressing the expression of TAL1 target genes (PubMed:19799863). Required for the maintenance of the secretory cell lineage in the small intestine (PubMed:16227606). Can inhibit Notch signaling probably by association with RBPJ and may be involved in GFI1-mediated Paneth cell differentiation (PubMed:25398765).[UniProtKB:O43439]^[2] ^[3] ^[4]

References

↑ Barrett CW, Fingleton B, Williams A, Ning W, Fischer MA, Washington MK, Chaturvedi R, Wilson KT, Hiebert SW, Williams CS. MTGR1 is required for tumorigenesis in the murine AOM/DSS colitis-associated carcinoma model. Cancer Res. 2011 Feb 15;71(4):1302-12. PMID:21303973 doi:10.1158/0008-5472.CAN-10-3317
↑ Amann JM, Chyla BJ, Ellis TC, Martinez A, Moore AC, Franklin JL, McGhee L, Meyers S, Ohm JE, Luce KS, Ouelette AJ, Washington MK, Thompson MA, King D, Gautam S, Coffey RJ, Whitehead RH, Hiebert SW. Mtgr1 is a transcriptional corepressor that is required for maintenance of the secretory cell lineage in the small intestine. Mol Cell Biol. 2005 Nov;25(21):9576-85. PMID:16227606 doi:10.1128/MCB.25.21.9576-9585.2005
↑ Parang B, Rosenblatt D, Williams AD, Washington MK, Revetta F, Short SP, Reddy VK, Hunt A, Shroyer NF, Engel ME, Hiebert SW, Williams CS. The transcriptional corepressor MTGR1 regulates intestinal secretory lineage allocation. FASEB J. 2015 Mar;29(3):786-95. PMID:25398765 doi:10.1096/fj.14-254284
↑ Tu S, Narendra V, Yamaji M, Vidal SE, Rojas LA, Wang X, Kim SY, Garcia BA, Tuschl T, Stadtfeld M, Reinberg D. Co-repressor CBFA2T2 regulates pluripotency and germline development. Nature. 2016 Jun 16;534(7607):387-90. PMID:27281218 doi:10.1038/nature18004

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OCA

[1] Barrett CW, Fingleton B, Williams A, Ning W, Fischer MA, Washington MK, Chaturvedi R, Wilson KT, Hiebert SW, Williams CS. MTGR1 is required for tumorigenesis in the murine AOM/DSS colitis-associated carcinoma model. Cancer Res. 2011 Feb 15;71(4):1302-12. PMID:21303973 doi:10.1158/0008-5472.CAN-10-3317

[2] Amann JM, Chyla BJ, Ellis TC, Martinez A, Moore AC, Franklin JL, McGhee L, Meyers S, Ohm JE, Luce KS, Ouelette AJ, Washington MK, Thompson MA, King D, Gautam S, Coffey RJ, Whitehead RH, Hiebert SW. Mtgr1 is a transcriptional corepressor that is required for maintenance of the secretory cell lineage in the small intestine. Mol Cell Biol. 2005 Nov;25(21):9576-85. PMID:16227606 doi:10.1128/MCB.25.21.9576-9585.2005

[3] Parang B, Rosenblatt D, Williams AD, Washington MK, Revetta F, Short SP, Reddy VK, Hunt A, Shroyer NF, Engel ME, Hiebert SW, Williams CS. The transcriptional corepressor MTGR1 regulates intestinal secretory lineage allocation. FASEB J. 2015 Mar;29(3):786-95. PMID:25398765 doi:10.1096/fj.14-254284

[4] Tu S, Narendra V, Yamaji M, Vidal SE, Rojas LA, Wang X, Kim SY, Garcia BA, Tuschl T, Stadtfeld M, Reinberg D. Co-repressor CBFA2T2 regulates pluripotency and germline development. Nature. 2016 Jun 16;534(7607):387-90. PMID:27281218 doi:10.1038/nature18004

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9k22

A novel histone H3K27 reader, CBFA2T2, inhibits H3K27me3 demethylation and tumor growth by regulating metabolic genes and metabolite levels

Structural highlights

Disease

Function

References

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