title: Effects of HMGN variants on the cellular transcription profile.
abstract: High mobility group N (HMGN) is a family of intrinsically disordered nuclear proteins that bind to nucleosomes, alters the structure of chromatin and affects transcription. A major unresolved question is the extent of functional specificity, or redundancy, between the various members of the HMGN protein family. Here, we analyze the transcriptional profile of cells in which the expression of various HMGN proteins has been either deleted or doubled. We find that both up- and downregulation of HMGN expression altered the cellular transcription profile. Most, but not all of the changes were variant specific, suggesting limited redundancy in transcriptional regulation. Analysis of point and swap HMGN mutants revealed that the transcriptional specificity is determined by a unique combination of a functional nucleosome-binding domain and C-terminal domain. Doubling the amount of HMGN had a significantly larger effect on the transcription profile than total deletion, suggesting that the intrinsically disordered structure of HMGN proteins plays an important role in their function. The results reveal an HMGN-variant-specific effect on the fidelity of the cellular transcription profile, indicating that functionally the various HMGN subtypes are not fully redundant.
authors.affiliation: Protein Section, Laboratory of Metabolism, Center for Cancer Research, National Cancer Institute, Computational Biology Branch, National Center for Biotechnology Information, National Library of Medicine, National Institutes of Health, 9000 Rockville Pike, Bethesda, MD 20894, USA.
authors.forename: Mark
authors.initials: M
authors.lastname: Rochman
authors.forename: Leila
authors.initials: L
authors.lastname: Taher
authors.forename: Toshihiro
authors.initials: T
authors.lastname: Kurahashi
authors.forename: Srujana
authors.initials: S
authors.lastname: Cherukuri
authors.forename: Vladimir N
authors.initials: VN
authors.lastname: Uversky
authors.forename: David
authors.initials: D
authors.lastname: Landsman
authors.forename: Ivan
authors.initials: I
authors.lastname: Ovcharenko
authors.forename: Michael
authors.initials: M
authors.lastname: Bustin
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D024001:HMGN Proteins / Q000737:chemistry / Q000235:genetics / Q000502:physiology*; D051379:Mice; D018345:Mice, Knockout; D008969:Molecular Sequence Data; D009154:Mutation; D017386:Sequence Homology, Amino Acid; D014158:Transcription, Genetic
chemical_list: D024001:HMGN Proteins