title: Down-regulation of nucleosomal binding protein HMGN1 expression during embryogenesis modulates Sox9 expression in chondrocytes.
abstract: We find that during embryogenesis the expression of HMGN1, a nuclear protein that binds to nucleosomes and reduces the compaction of the chromatin fiber, is progressively down-regulated throughout the entire embryo, except in committed but continuously renewing cell types, such as the basal layer of the epithelium. In the developing limb bud, the expression of HMGN1 is complementary to Sox9, a master regulator of the chondrocyte lineage. In limb bud micromass cultures, which faithfully mimic in vivo chondrogenic differentiation, loss of HMGN1 accelerates differentiation. Expression of wild-type HMGN1, but not of a mutant HMGN1 that does not bind to chromatin, in Hmgn1-/- micromass cultures inhibits Sox9 expression and retards differentiation. Chromatin immunoprecipitation analysis reveals that HMGN1 binds to Sox9 chromatin in cells that are poised to express Sox9. Loss of HMGN1 elevates the amount of HMGN2 bound to Sox9, suggesting functional redundancy among these proteins. These findings suggest a role for HMGN1 in chromatin remodeling during embryogenesis and in the activation of Sox9 during chondrogenesis.
authors.affiliation: Protein Section, Laboratory of Metabolism, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Building 37, Room 3122, 9000 Rockville Pike, Bethesda, Maryland 20892, USA.
authors.forename: Takashi
authors.initials: T
authors.lastname: Furusawa
authors.forename: Jae-Hwan
authors.initials: JH
authors.lastname: Lim
authors.forename: Frédéric
authors.initials: F
authors.lastname: Catez
authors.forename: Yehudit
authors.initials: Y
authors.lastname: Birger
authors.forename: Susan
authors.initials: S
authors.lastname: Mackem
authors.forename: Michael
authors.initials: M
authors.lastname: Bustin
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000502:physiology; D002478:Cells, Cultured; D019902:Chondrocytes / Q000378:metabolism / Q000502:physiology*; D002843:Chromatin / Q000378:metabolism; D015536:Down-Regulation; D047108:Embryonic Development; D024241:HMGN1 Protein / Q000096:biosynthesis* / Q000235:genetics; D024242:HMGN2 Protein / Q000235:genetics / Q000378:metabolism; D006609:High Mobility Group Proteins / Q000096:biosynthesis* / Q000235:genetics; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D018878:Limb Buds / Q000166:cytology / Q000196:embryology / Q000378:metabolism; D051379:Mice; D009154:Mutation; D009707:Nucleosomes / Q000378:metabolism*; D055758:SOX9 Transcription Factor; D046509:Tissue Culture Techniques; D014157:Transcription Factors / Q000096:biosynthesis* / Q000235:genetics
chemical_list: D002843:Chromatin; D024241:HMGN1 Protein; D024242:HMGN2 Protein; D006609:High Mobility Group Proteins; D009707:Nucleosomes; D055758:SOX9 Transcription Factor; C527933:Sox9 protein, mouse; D014157:Transcription Factors