| Structural highlights
Function
[SP16H_HUMAN] Component of the FACT complex, a general chromatin factor that acts to reorganize nucleosomes. The FACT complex is involved in multiple processes that require DNA as a template such as mRNA elongation, DNA replication and DNA repair. During transcription elongation the FACT complex acts as a histone chaperone that both destabilizes and restores nucleosomal structure. It facilitates the passage of RNA polymerase II and transcription by promoting the dissociation of one histone H2A-H2B dimer from the nucleosome, then subsequently promotes the reestablishment of the nucleosome following the passage of RNA polymerase II. The FACT complex is probably also involved in phosphorylation of 'Ser-392' of p53/TP53 via its association with CK2 (casein kinase II).[1] [2] [3] [4] [5] [6]
Publication Abstract from PubMed
FACT (Facilitates Chromatin Transactions) is a heterodimeric protein complex involved in RNA polymerase II transcription elongation, playing essential roles in chromatin remodeling during transcription, replication, and DNA damage repair. The FACT subunit hSpt16 is essential for nucleosome reorganization. The N-terminal domain of hSpt16 (hSpt16-NTD) was recently described as a histone (H3-H4)2-binding domain; however, its mode of interaction remains unknown. In this study, we solved the structure of hSpt16-NTD437 at 2.19A and found that a long-disordered region (hSpt16-LDR), after the main body of hSpt16-NTD, is a novel histone-binding motif. Furthermore, hSpt16-LDR interaction with (H3-H4)2 is H3 N-terminal tail-independent. Therefore, Spt16-NTD is a histone H3-H4-specific binding domain with a distinct mechanism of interaction between histones and histone chaperones.
The structural basis of human Spt16N-terminal domain interaction with histone (H3-H4)2 tetramer.,Jiang H, Xu S, Chen Y, Li H, Tian L, Zhou H, Zhao Z, Yang C, Zhong Z, Cai G, Su D Biochem Biophys Res Commun. 2019 Jan 15;508(3):864-870. doi:, 10.1016/j.bbrc.2018.11.150. Epub 2018 Dec 7. PMID:30528735[7]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Wada T, Orphanides G, Hasegawa J, Kim DK, Shima D, Yamaguchi Y, Fukuda A, Hisatake K, Oh S, Reinberg D, Handa H. FACT relieves DSIF/NELF-mediated inhibition of transcriptional elongation and reveals functional differences between P-TEFb and TFIIH. Mol Cell. 2000 Jun;5(6):1067-72. PMID:10912001
- ↑ Keller DM, Zeng X, Wang Y, Zhang QH, Kapoor M, Shu H, Goodman R, Lozano G, Zhao Y, Lu H. A DNA damage-induced p53 serine 392 kinase complex contains CK2, hSpt16, and SSRP1. Mol Cell. 2001 Feb;7(2):283-92. PMID:11239457
- ↑ Belotserkovskaya R, Oh S, Bondarenko VA, Orphanides G, Studitsky VM, Reinberg D. FACT facilitates transcription-dependent nucleosome alteration. Science. 2003 Aug 22;301(5636):1090-3. PMID:12934006 doi:http://dx.doi.org/10.1126/science.1085703
- ↑ Pavri R, Zhu B, Li G, Trojer P, Mandal S, Shilatifard A, Reinberg D. Histone H2B monoubiquitination functions cooperatively with FACT to regulate elongation by RNA polymerase II. Cell. 2006 May 19;125(4):703-17. PMID:16713563 doi:http://dx.doi.org/S0092-8674(06)00570-8
- ↑ Orphanides G, LeRoy G, Chang CH, Luse DS, Reinberg D. FACT, a factor that facilitates transcript elongation through nucleosomes. Cell. 1998 Jan 9;92(1):105-16. PMID:9489704
- ↑ LeRoy G, Orphanides G, Lane WS, Reinberg D. Requirement of RSF and FACT for transcription of chromatin templates in vitro. Science. 1998 Dec 4;282(5395):1900-4. PMID:9836642
- ↑ Jiang H, Xu S, Chen Y, Li H, Tian L, Zhou H, Zhao Z, Yang C, Zhong Z, Cai G, Su D. The structural basis of human Spt16N-terminal domain interaction with histone (H3-H4)2 tetramer. Biochem Biophys Res Commun. 2019 Jan 15;508(3):864-870. doi:, 10.1016/j.bbrc.2018.11.150. Epub 2018 Dec 7. PMID:30528735 doi:http://dx.doi.org/10.1016/j.bbrc.2018.11.150
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