H3.Y discriminates between HIRA and DAXX chaperone complexes and reveals unexpected insights into human DAXX-H3.3-H4 binding and deposition requirements
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H3.Y discriminates between HIRA and DAXX chaperone complexes and reveals unexpected insights into human DAXX-H3.3-H4 binding and deposition requirements. / Zink, Lisa-Maria; Delbarre, Erwan; Eberl, H Christian; Keilhauer, Eva C; Bönisch, Clemens; Pünzeler, Sebastian; Bartkuhn, Marek; Collas, Philippe; Mann, Matthias; Hake, Sandra B.
In: Nucleic Acids Research, Vol. 45, No. 10, 02.06.2017, p. 5691-5706.Research output: Contribution to journal › Journal article › Research › peer-review
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T1 - H3.Y discriminates between HIRA and DAXX chaperone complexes and reveals unexpected insights into human DAXX-H3.3-H4 binding and deposition requirements
AU - Zink, Lisa-Maria
AU - Delbarre, Erwan
AU - Eberl, H Christian
AU - Keilhauer, Eva C
AU - Bönisch, Clemens
AU - Pünzeler, Sebastian
AU - Bartkuhn, Marek
AU - Collas, Philippe
AU - Mann, Matthias
AU - Hake, Sandra B
N1 - © The Author(s) 2017. Published by Oxford University Press on behalf of Nucleic Acids Research.
PY - 2017/6/2
Y1 - 2017/6/2
N2 - Histone chaperones prevent promiscuous histone interactions before chromatin assembly. They guarantee faithful deposition of canonical histones and functionally specialized histone variants into chromatin in a spatial- and temporally-restricted manner. Here, we identify the binding partners of the primate-specific and H3.3-related histone variant H3.Y using several quantitative mass spectrometry approaches, and biochemical and cell biological assays. We find the HIRA, but not the DAXX/ATRX, complex to recognize H3.Y, explaining its presence in transcriptionally active euchromatic regions. Accordingly, H3.Y nucleosomes are enriched in the transcription-promoting FACT complex and depleted of repressive post-translational histone modifications. H3.Y mutational gain-of-function screens reveal an unexpected combinatorial amino acid sequence requirement for histone H3.3 interaction with DAXX but not HIRA, and for H3.3 recruitment to PML nuclear bodies. We demonstrate the importance and necessity of specific H3.3 core and C-terminal amino acids in discriminating between distinct chaperone complexes. Further, chromatin immunoprecipitation sequencing experiments reveal that in contrast to euchromatic HIRA-dependent deposition sites, human DAXX/ATRX-dependent regions of histone H3 variant incorporation are enriched in heterochromatic H3K9me3 and simple repeat sequences. These data demonstrate that H3.Y's unique amino acids allow a functional distinction between HIRA and DAXX binding and its consequent deposition into open chromatin.
AB - Histone chaperones prevent promiscuous histone interactions before chromatin assembly. They guarantee faithful deposition of canonical histones and functionally specialized histone variants into chromatin in a spatial- and temporally-restricted manner. Here, we identify the binding partners of the primate-specific and H3.3-related histone variant H3.Y using several quantitative mass spectrometry approaches, and biochemical and cell biological assays. We find the HIRA, but not the DAXX/ATRX, complex to recognize H3.Y, explaining its presence in transcriptionally active euchromatic regions. Accordingly, H3.Y nucleosomes are enriched in the transcription-promoting FACT complex and depleted of repressive post-translational histone modifications. H3.Y mutational gain-of-function screens reveal an unexpected combinatorial amino acid sequence requirement for histone H3.3 interaction with DAXX but not HIRA, and for H3.3 recruitment to PML nuclear bodies. We demonstrate the importance and necessity of specific H3.3 core and C-terminal amino acids in discriminating between distinct chaperone complexes. Further, chromatin immunoprecipitation sequencing experiments reveal that in contrast to euchromatic HIRA-dependent deposition sites, human DAXX/ATRX-dependent regions of histone H3 variant incorporation are enriched in heterochromatic H3K9me3 and simple repeat sequences. These data demonstrate that H3.Y's unique amino acids allow a functional distinction between HIRA and DAXX binding and its consequent deposition into open chromatin.
KW - Adaptor Proteins, Signal Transducing
KW - Amino Acid Sequence
KW - Animals
KW - Binding Sites
KW - Cell Cycle Proteins
KW - Cell Line, Transformed
KW - Chromatin
KW - DNA-Binding Proteins
KW - Epithelial Cells
KW - HeLa Cells
KW - High Mobility Group Proteins
KW - Histone Chaperones
KW - Histone Code
KW - Histones
KW - Humans
KW - Mesenchymal Stromal Cells
KW - Microsatellite Repeats
KW - Nuclear Proteins
KW - Nucleosomes
KW - Primary Cell Culture
KW - Protein Binding
KW - Sequence Alignment
KW - Sequence Homology, Amino Acid
KW - Transcription Factors
KW - Transcription, Genetic
KW - Transcriptional Elongation Factors
KW - Journal Article
U2 - 10.1093/nar/gkx131
DO - 10.1093/nar/gkx131
M3 - Journal article
C2 - 28334823
VL - 45
SP - 5691
EP - 5706
JO - Nucleic Acids Research
JF - Nucleic Acids Research
SN - 0305-1048
IS - 10
ER -
ID: 184292133