Redundant Functions for Nap1 and Chz1 in H2A.Z Deposition.

Autor: Dronamraju R; Department of Biochemistry and Biophysics, University of North Carolina at Chapel Hill, Chapel Hill, NC, 27599, USA., Ramachandran S; Department of Biochemistry and Biophysics, University of North Carolina at Chapel Hill, Chapel Hill, NC, 27599, USA.; Division of Basic Sciences, Fred Hutchinson Cancer Research Center, Seattle, WA, 98109, USA., Jha DK; Department of Biochemistry and Biophysics, University of North Carolina at Chapel Hill, Chapel Hill, NC, 27599, USA.; Division of Hematology/Oncology, Department of Medicine, Children's Hospital Boston, Boston, MA, USA., Adams AT; Department of Biochemistry and Biophysics, University of North Carolina at Chapel Hill, Chapel Hill, NC, 27599, USA., DiFiore JV; Curriculum in Genetics and Molecular Biology, University of North Carolina, Chapel Hill, NC, 27599, USA., Parra MA; Department Susquehanna University, Selinsgrove, PA, 17870, USA., Dokholyan NV; Department of Biochemistry and Biophysics, University of North Carolina at Chapel Hill, Chapel Hill, NC, 27599, USA. dokh@unc.edu.; Program in Molecular and Cellular Biophysics, University of North Carolina at Chapel Hill, Chapel Hill, NC, 27599, USA. dokh@unc.edu.; Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC, 27599, USA. dokh@unc.edu., Strahl BD; Department of Biochemistry and Biophysics, University of North Carolina at Chapel Hill, Chapel Hill, NC, 27599, USA. brian_strahl@med.unc.edu.; Curriculum in Genetics and Molecular Biology, University of North Carolina, Chapel Hill, NC, 27599, USA. brian_strahl@med.unc.edu.; Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC, 27599, USA. brian_strahl@med.unc.edu.
Jazyk: angličtina
Zdroj: Scientific reports [Sci Rep] 2017 Sep 07; Vol. 7 (1), pp. 10791. Date of Electronic Publication: 2017 Sep 07.
DOI: 10.1038/s41598-017-11003-8
Abstrakt: H2A.Z is a histone H2A variant that contributes to transcriptional regulation, DNA damage response and limits heterochromatin spreading. In Saccharomyces cerevisiae, H2A.Z is deposited by the SWR-C complex, which relies on several histone chaperones including Nap1 and Chz1 to deliver H2A.Z-H2B dimers to SWR-C. However, the mechanisms by which Nap1 and Chz1 cooperate to bind H2A.Z and their contribution to H2A.Z deposition in chromatin is not well understood. Using structural modeling and molecular dynamics simulations, we identify a series of H2A.Z residues that form a chaperone-specific binding surface. Mutation of these residues revealed different surface requirements for Nap1 and Chz1 interaction with H2A.Z. Consistent with this result, we found that loss of Nap1 or Chz1 individually resulted in mild defects in H2A.Z deposition, but that deletion of both Nap1 and Chz1 resulted in a significant reduction of H2A.Z deposition at promoters and led to heterochromatin spreading. Together, our findings reveal unique H2A.Z surface dependences for Nap1 and Chz1 and a redundant role for these chaperones in H2A.Z deposition.
Databáze: MEDLINE