The interaction of NSBP1/HMGN5 with nucleosomes in euchromatin counteracts linker histone-mediated chromatin compaction and modulates transcription.
Structural changes in specific chromatin domains are essential to the orderly progression of numerous nuclear processes, including transcription. We report that the nuclear protein NSBP1 (HMGN5), a recently discovered member of the HMGN nucleosome-binding protein family, is specifically targeted by its C-terminal domain to nucleosomes in euchromatin. We find that the interaction of NSBP1 with nucleosomes alters the compaction of cellular chromatin and that in living cells, NSBP1 interacts with linker histones. We demonstrate that the negatively charged C-terminal domain of NSBP1 interacts with the positively charged C-terminal domain of H5 and that NSBP1 counteracts the linker histone-mediated compaction of a nucleosomal array. Dysregulation of the cellular levels of NSBP1 alters the transcription level of numerous genes. We suggest that mouse NSBP1 is an architectural protein that binds preferentially to euchromatin and modulates the fidelity of the cellular transcription profile by counteracting the chromatin-condensing activity of linker histones.
Rochman
Mark
M
Protein Section, Laboratory of Metabolism, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA.
Postnikov
Yuri
Y
Correll
Sarah
S
Malicet
Cedric
C
Wincovitch
Stephen
S
Karpova
Tatiana S
TS
McNally
James G
JG
Wu
Xiaolin
X
Bubunenko
Nina A
NA
Grigoryev
Sergei
S
Bustin
Michael
M
D000818:Animals; D001665:Binding Sites; D002461:Cell Line, Transformed; D042002:Chromatin Assembly and Disassembly; D022041:Euchromatin / Q000737:chemistry / Q000378:metabolism*; D020869:Gene Expression Profiling; D024001:HMGN Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D006657:Histones / Q000737:chemistry / Q000378:metabolism*; D008239:Lysine; D008745:Methylation; D051379:Mice; D018613:Microscopy, Confocal; D008958:Models, Molecular; D041681:NIH 3T3 Cells; D009690:Nucleic Acid Conformation; D009707:Nucleosomes / Q000378:metabolism*; D011487:Protein Conformation; D011499:Protein Processing, Post-Translational; D017434:Protein Structure, Tertiary; D034622:RNA Interference; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D015534:Trans-Activators / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D014158:Transcription, Genetic; D014162:Transfection
D022041:Euchromatin; D024001:HMGN Proteins; D006657:Histones; C498963:Hmgn5 protein, mouse; D009707:Nucleosomes; D011993:Recombinant Fusion Proteins; D015534:Trans-Activators; D008239:Lysine