Chromosomal protein HMGN1 modulates histone H3 phosphorylation.
Here we demonstrate that HMGN1, a nuclear protein that binds to nucleosomes and reduces the compaction of the chromatin fiber, modulates histone posttranslational modifications. In Hmgn1-/- cells, loss of HMGN1 elevates the steady-state levels of phospho-S10-H3 and enhances the rate of stress-induced phosphorylation of S10-H3. In vitro, HMGN1 reduces the rate of phospho-S10-H3 by hindering the ability of kinases to modify nucleosomal, but not free, H3. During anisomycin treatment, the phosphorylation of HMGN1 precedes that of H3 and leads to a transient weakening of the binding of HMGN1 to chromatin. We propose that the reduced binding of HMGN1 to nucleosomes, or the absence of the protein, improves access of anisomysin-induced kinases to H3. Thus, the levels of posttranslational modifications in chromatin are modulated by nucleosome binding proteins that alter the ability of enzymatic complexes to access and modify their nucleosomal targets.
Laboratory of Metabolism, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA.
Jae-Hwan
JH
Lim
Frédéric
F
Catez
Yehudit
Y
Birger
Katherine L
KL
West
Marta
M
Prymakowska-Bosak
Yuri V
YV
Postnikov
Michael
M
Bustin
D000818:Animals; D000841:Anisomycin / Q000494:pharmacology; D002478:Cells, Cultured; D002843:Chromatin / Q000378:metabolism; D005347:Fibroblasts / Q000166:cytology / Q000187:drug effects / Q000502:physiology; D005786:Gene Expression Regulation; D017781:Genes, Immediate-Early; D024241:HMGN1 Protein / Q000235:genetics / Q000378:metabolism*; D006657:Histones / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D009707:Nucleosomes / Q000378:metabolism; D010766:Phosphorylation; D011485:Protein Binding; D011499:Protein Processing, Post-Translational; D011500:Protein Synthesis Inhibitors / Q000494:pharmacology
D002843:Chromatin; D024241:HMGN1 Protein; D006657:Histones; D009707:Nucleosomes; D011500:Protein Synthesis Inhibitors; D000841:Anisomycin