Redundant Functions for Nap1 and Chz1 in H2A.Z Deposition

Raghuvar Dronamraju, Srinivas Ramachandran, Deepak K. Jha, Alexander T. Adams, Julia V. Difiore, Michael A. Parra, Nikolay V. Dokholyan, Brian D. Strahl

Research output: Contribution to journalArticle

4 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Article number10791
JournalScientific reports
Volume7
Issue number1
DOIs
StatePublished - Dec 1 2017

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Heterochromatin
Histone Chaperones
Molecular Dynamics Simulation
Histones
DNA Damage
Chromatin
Saccharomyces cerevisiae
Mutation

All Science Journal Classification (ASJC) codes

  • General

Cite this

Dronamraju, R., Ramachandran, S., Jha, D. K., Adams, A. T., Difiore, J. V., Parra, M. A., ... Strahl, B. D. (2017). Redundant Functions for Nap1 and Chz1 in H2A.Z Deposition. Scientific reports, 7(1), [10791]. https://doi.org/10.1038/s41598-017-11003-8
Dronamraju, Raghuvar ; Ramachandran, Srinivas ; Jha, Deepak K. ; Adams, Alexander T. ; Difiore, Julia V. ; Parra, Michael A. ; Dokholyan, Nikolay V. ; Strahl, Brian D. / Redundant Functions for Nap1 and Chz1 in H2A.Z Deposition. In: Scientific reports. 2017 ; Vol. 7, No. 1.
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Dronamraju, R, Ramachandran, S, Jha, DK, Adams, AT, Difiore, JV, Parra, MA, Dokholyan, NV & Strahl, BD 2017, 'Redundant Functions for Nap1 and Chz1 in H2A.Z Deposition', Scientific reports, vol. 7, no. 1, 10791. https://doi.org/10.1038/s41598-017-11003-8

Redundant Functions for Nap1 and Chz1 in H2A.Z Deposition. / Dronamraju, Raghuvar; Ramachandran, Srinivas; Jha, Deepak K.; Adams, Alexander T.; Difiore, Julia V.; Parra, Michael A.; Dokholyan, Nikolay V.; Strahl, Brian D.

In: Scientific reports, Vol. 7, No. 1, 10791, 01.12.2017.

Research output: Contribution to journalArticle

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T1 - Redundant Functions for Nap1 and Chz1 in H2A.Z Deposition

AU - Dronamraju, Raghuvar

AU - Ramachandran, Srinivas

AU - Jha, Deepak K.

AU - Adams, Alexander T.

AU - Difiore, Julia V.

AU - Parra, Michael A.

AU - Dokholyan, Nikolay V.

AU - Strahl, Brian D.

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AB - 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.

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Dronamraju R, Ramachandran S, Jha DK, Adams AT, Difiore JV, Parra MA et al. Redundant Functions for Nap1 and Chz1 in H2A.Z Deposition. Scientific reports. 2017 Dec 1;7(1). 10791. https://doi.org/10.1038/s41598-017-11003-8