Nature | Vol 577 | 16 January 2020 | 431
Both processes might be facilitated by the HMG domain of SSRP1^24
and other domains not visible in our structure, and this is the topic of
ongoing investigations.
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- Orphanides, G., LeRoy, G., Chang, C. H., Luse, D. S. & Reinberg, D. FACT, a factor
that facilitates transcript elongation through nucleosomes. Cell 92 , 105–116
(1998). - Gurova, K., Chang, H. W., Valieva, M. E., Sandlesh, P. & Studitsky, V. M. Structure and
function of the histone chaperone FACT—resolving FACTual issues. Biochim. Biophys.
Acta. Gene Regul. Mech. 1861 , 892–904 (2018). - Wang, T. et al. The histone chaperone FACT modulates nucleosome structure by
tethering its components. Life Sci Alliance 1 , e201800107 (2018). - Luger, K., Mäder, A. W., Richmond, R. K., Sargent, D. F. & Richmond, T. J. Crystal
structure of the nucleosome core particle at 2.8 Å resolution. Nature 389 , 251–260
(1997). - Lai, W. K. M. & Pugh, B. F. Understanding nucleosome dynamics and their links to gene
expression and DNA replication. Nat. Rev. Mol. Cell Biol. 18 , 548–562 (2017). - Das, C., Tyler, J. K. & Churchill, M. E. The histone shuffle: histone chaperones in an
energetic dance. Trends Biochem. Sci. 35 , 476–489 (2010). - Belotserkovskaya, R. et al. FACT facilitates transcription-dependent nucleosome
alteration. Science 301 , 1090–1093 (2003). - Hsieh, F. K. et al. Histone chaperone FACT action during transcription through chromatin
by RNA polymerase II. Proc. Natl Acad. Sci. USA 110 , 7654–7659 (2013). - Winkler, D. D., Muthurajan, U. M., Hieb, A. R. & Luger, K. Histone chaperone FACT
coordinates nucleosome interaction through multiple synergistic binding events. J. Biol.
Chem. 286 , 41883–41892 (2011).
10. Tsunaka, Y., Fujiwara, Y., Oyama, T., Hirose, S. & Morikawa, K. Integrated molecular
mechanism directing nucleosome reorganization by human FACT. Genes Dev. 30 ,
673–686 (2016).
11. Valieva, M. E. et al. Large-scale ATP-independent nucleosome unfolding by a histone
chaperone. Nat. Struct. Mol. Biol. 23 , 1111–1116 (2016).
12. Kemble, D. J., McCullough, L. L., Whitby, F. G., Formosa, T. & Hill, C. P. FACT disrupts
nucleosome structure by binding H2A-H2B with conserved peptide motifs. Mol. Cell 60 ,
294–306 (2015).
13. Chen, P. et al. Functions of FACT in breaking the nucleosome and maintaining its integrity
at the single-nucleosome level. Mol. Cell 71 , 284–293 (2018).
14. Dandey, V. P. et al. Spotiton: new features and applications. J. Struct. Biol. 202 , 161–169
(2018).
15. Tachiwana, H. et al. Structural basis of instability of the nucleosome containing a testis-
specific histone variant, human H3T. Proc. Natl Acad. Sci. USA 107 , 10454–10459 (2010).
16. Hageman, T. S. & Weis, D. D. Reliable identification of significant differences in differential
hydrogen exchange-mass spectrometry measurements using a hybrid significance
testing approach. Anal. Chem. 91 , 8008–8016 (2019).
17. D’Arcy, S. et al. Chaperone Nap1 shields histone surfaces used in a nucleosome and can
put H2A-H2B in an unconventional tetrameric form. Mol. Cell 51 , 662–677 (2013).
18. Kujirai, T. et al. Structural basis of the nucleosome transition during RNA polymerase II
passage. Science 362 , 595–598 (2018).
19. Ehara, H. et al. Structural insight into nucleosome transcription by RNA polymerase II with
elongation factors. Science 363 , 744–747 (2019).
20. Hondele, M. et al. Structural basis of histone H2A–H2B recognition by the essential
chaperone FACT. Nature 499 , 111–114 (2013).
21. Zhang, W. et al. Crystal structure of human SSRP1 middle domain reveals a role in DNA
binding. Sci. Rep. 5 , 18688 (2015).
22. Mayanagi, K. et al. Structural visualization of key steps in nucleosome reorganization by
human FACT. Sci. Rep. 9 , 10183 (2019).
23. Ramachandran, S., Ahmad, K. & Henikoff, S. Transcription and remodeling produce
asymmetrically unwrapped nucleosomal intermediates. Mol. Cell 68 , 1038–1053
(2017).
24. McCullough, L. L. et al. Functional roles of the DNA-binding HMGB domain in the histone
chaperone FACT in nucleosome reorganization. J. Biol. Chem. 293 , 6121–6133 (2018).
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