6wmi

Structural highlights

Function

ZN410_HUMAN Transcription factor that binds to the sequence motif 5'-CATCCCATAATA-3', and is specifically required to silence expression of fetal hemoglobin in adult erythroid cells (PubMed:33859416, PubMed:33301730). Prevents expression of fetal hemoglobin genes HBG1 and HBG2 through CHD4: acts as a direct transcriptional activator of CHD4, a central component of the NuRD complex that represses transcription of fetal hemoglobin genes HBG1 and HBG2 in erythroid cells (PubMed:33859416, PubMed:33301730). May also activate transcription of matrix-remodeling genes such as MMP1 during fibroblast senescence (PubMed:12370286). May activate transcription of the gap junction gene GJC1, perhaps in response to increasing glucose (PubMed:30078215). However, recent studies suggest that ZNF410 is dedicated to regulate expression of a single gene: CHD4 (PubMed:33859416, PubMed:33301730).^{[1] [2] [3] [4]}

References

1. ↑ Benanti JA, Williams DK, Robinson KL, Ozer HL, Galloway DA. Induction of extracellular matrix-remodeling genes by the senescence-associated protein APA-1. Mol Cell Biol. 2002 Nov;22(21):7385-97. PMID:12370286 doi:10.1128/MCB.22.21.7385-7397.2002
2. ↑ Chen Y, Liu R, Chu Z, Le B, Zeng H, Zhang X, Wu Q, Zhu G, Chen Y, Liu Y, Sun F, Lu Z, Qiao Y, Wang J. High glucose stimulates proliferative capacity of liver cancer cells possibly via O-GlcNAcylation-dependent transcriptional regulation of GJC1. J Cell Physiol. 2018 Jan;234(1):606-618. PMID:30078215 doi:10.1002/jcp.26803
3. ↑ Lan X, Ren R, Feng R, Ly LC, Lan Y, Zhang Z, Aboreden N, Qin K, Horton JR, Grevet JD, Mayuranathan T, Abdulmalik O, Keller CA, Giardine B, Hardison RC, Crossley M, Weiss MJ, Cheng X, Shi J, Blobel GA. ZNF410 Uniquely Activates the NuRD Component CHD4 to Silence Fetal Hemoglobin Expression. Mol Cell. 2021 Jan 21;81(2):239-254.e8. PMID:33301730 doi:10.1016/j.molcel.2020.11.006
4. ↑ Vinjamur DS, Yao Q, Cole MA, McGuckin C, Ren C, Zeng J, Hossain M, Luk K, Wolfe SA, Pinello L, Bauer DE. ZNF410 represses fetal globin by singular control of CHD4. Nat Genet. 2021 May;53(5):719-728. PMID:33859416 doi:10.1038/s41588-021-00843-w