In molecular biology, HOTTIP (HOXA transcript at the distal tip) is a long non-coding RNA. The gene encoding HOTTIP is located at the 5′ tip of the HOXA locus, and coordinates the activation of several of the 5′ HOXA genes. The non-coding RNA is brought into close proximity with the HOXA genes by chromosomal looping. HOTTIP binds to the WDR5 protein, which forms a complex with the histone methyltransferase protein MLL. This targets the WDR5-MLL complex to the HOXA region and results in H3K4 methylation and transcriptional activation of the HOXA locus.[1] More recently, HOTTIP has been shown to play a role in Hepatocellular Carcinoma (HCC) progression. HOTTIP expression levels predict metastasis formation and poor disease outcome in HCC patients. [2] HOTTIP has been shown to be transcriptionally regulated by a transcriptional coactivator PSIP1/p52[3]
See also
editReferences
edit- ^ Wang KC, Yang YW, Liu B, Sanyal A, Corces-Zimmerman R, Chen Y, et al. (2011). "A long noncoding RNA maintains active chromatin to coordinate homeotic gene expression". Nature. 472 (7341): 120–124. Bibcode:2011Natur.472..120W. doi:10.1038/nature09819. PMC 3670758. PMID 21423168.
- ^ Quagliata, L; Matter, MS; Piscuoglio, S; Arabi, L; Ruiz, C; Procino, A; Kovac, M; Moretti, F; Makowska, Z; Boldanova, T; Andersen, JB; Hämmerle, M; Tornillo, L; Heim, MH; Diederichs, S; Cillo, C; Terracciano, LM (2014). "Long noncoding RNA HOTTIP/HOXA13 expression is associated with disease progression and predicts outcome in hepatocellular carcinoma patients". Hepatology. 59 (3): 911–23. doi:10.1002/hep.26740. PMC 3943759. PMID 24114970.
- ^ Pradeepa, Madapura M.; McKenna, Fionnuala; Taylor, Gillian C. A.; Bengani, Hemant; Grimes, Graeme R.; Wood, Andrew J.; Bhatia, Shipra; Bickmore, Wendy A. (2017-04-06). "Psip1/p52 regulates posterior Hoxa genes through activation of lncRNA Hottip". PLOS Genetics. 13 (4): e1006677. doi:10.1371/journal.pgen.1006677. ISSN 1553-7404. PMC 5383017. PMID 28384324.
Further reading
edit- Burgess DJ (2011). "Non-coding RNA: HOTTIP goes the distance". Nat Rev Genet. 12 (5): 300. doi:10.1038/nrg2992. PMID 21483457. S2CID 27802734.