TY - JOUR
T1 - Structural delineation of histone post-translation modifications in histone-nucleosome assembly protein complex
AU - Kumar, Anuj
AU - Kashyap, Maruthi
AU - Bhavesh, Neel Sarovar
AU - Yogavel, Manickam
AU - Sharma, Amit
PY - 2012/10
Y1 - 2012/10
N2 - Nucleosome assembly proteins (Nap) are histone chaperones with vital roles in chromatin assembly and disassembly. Decoding of histone post-translational modifications by histone chaperones is central in regulation of gene expression. We probed binding interfaces in Nap-histone complexes using histone peptide interaction arrays and chemical shift perturbation techniques. Phosphorylation at H3T32 and H3T118 enhanced Nap-peptide interactions while post-translational modifications like H3K122, H4K59 and H2AK36 diminished it. Nap recognition regions in histones H2A, H2B, H3 and H4 lie in core regions of the histone octamer, and form a surface exposed contiguous patch. Nap binding sites on H2A-H2B and H3-H4 fall on opposite surfaces of histone octamer, and the latter can therefore accommodate two dimeric Nap molecules simultaneously. Interfacial residues between Nap and histone octamer overlap with route of wrapped DNA on histone octamer, implying non-concurrent residency on the octamer by either Nap or DNA. Using NMR, we mapped Nap residues that undergo chemical shift perturbations in presence of histone peptides. Taken together, we provide an architectural model of a Nap-octamer complex which likely forms during chromatin reorganisation.
AB - Nucleosome assembly proteins (Nap) are histone chaperones with vital roles in chromatin assembly and disassembly. Decoding of histone post-translational modifications by histone chaperones is central in regulation of gene expression. We probed binding interfaces in Nap-histone complexes using histone peptide interaction arrays and chemical shift perturbation techniques. Phosphorylation at H3T32 and H3T118 enhanced Nap-peptide interactions while post-translational modifications like H3K122, H4K59 and H2AK36 diminished it. Nap recognition regions in histones H2A, H2B, H3 and H4 lie in core regions of the histone octamer, and form a surface exposed contiguous patch. Nap binding sites on H2A-H2B and H3-H4 fall on opposite surfaces of histone octamer, and the latter can therefore accommodate two dimeric Nap molecules simultaneously. Interfacial residues between Nap and histone octamer overlap with route of wrapped DNA on histone octamer, implying non-concurrent residency on the octamer by either Nap or DNA. Using NMR, we mapped Nap residues that undergo chemical shift perturbations in presence of histone peptides. Taken together, we provide an architectural model of a Nap-octamer complex which likely forms during chromatin reorganisation.
KW - Chromatin assembly
KW - Histone chaperone
KW - NMR spectroscopy
KW - Nucleosome assembly protein
KW - Peptide array
KW - Post-translational modification
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UR - http://www.scopus.com/inward/citedby.url?scp=84866998914&partnerID=8YFLogxK
U2 - 10.1016/j.jsb.2012.06.012
DO - 10.1016/j.jsb.2012.06.012
M3 - Article
C2 - 22771717
AN - SCOPUS:84866998914
SN - 1047-8477
VL - 180
SP - 1
EP - 9
JO - Journal of Structural Biology
JF - Journal of Structural Biology
IS - 1
ER -