title: Trichostatin-A induces differential changes in histone protein dynamics and expression in HeLa cells.
abstract: Trichostatin-A (TSA), a histone deacetylase (HDAC) inhibitor, results in enhanced acetylation of core histones thereby disrupting chromatin organization within living cells. We report on changes in chromatin organization and the resultant alteration in nuclear architecture following treatment with TSA using fluorescence imaging. TSA triggers an expected increase in the euchromatin fraction which is accompanied by a significant increase in nuclear volume and alterations in chromatin compaction mapped using fluorescence anisotropy imaging. We observe differential changes in the mobility of core and linker histones as measured by fluorescence recovery after photo-bleaching (FRAP) and fluorescence correlation spectroscopy (FCS) methods. Further TSA induces a differential increase in linker histone transcription and increased phosphorylation of linker histone proteins accompanying an expected increase in core histone acetylation patterns. Thus subtle feedback responses triggered by changes in chromatin configurations impinge selectively on linker histone mobility and its expression. These observations have implications for understanding the role of HDAC in the dynamic maintenance of chromatin organization.
authors.affiliation: SASTRA University, Tanjore 613402, India.
authors.forename: Jyothsna
authors.initials: J
authors.lastname: Rao
authors.forename: Dipanjan
authors.initials: D
authors.lastname: Bhattacharya
authors.forename: Bidisha
authors.initials: B
authors.lastname: Banerjee
authors.forename: Apurva
authors.initials: A
authors.lastname: Sarin
authors.forename: G V
authors.initials: GV
authors.lastname: Shivashankar
mesh_terms: D000107:Acetylation / Q000187:drug effects; D002843:Chromatin / Q000187:drug effects / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D005786:Gene Expression Regulation / Q000187:drug effects / Q000502:physiology*; D006367:HeLa Cells; D056572:Histone Deacetylase Inhibitors; D006655:Histone Deacetylases / Q000378:metabolism*; D006657:Histones / Q000378:metabolism*; D006801:Humans; D006877:Hydroxamic Acids / Q000008:administration & dosage*; D010766:Phosphorylation / Q000187:drug effects
chemical_list: D002843:Chromatin; D056572:Histone Deacetylase Inhibitors; D006657:Histones; D006877:Hydroxamic Acids; C012589:trichostatin A; D006655:Histone Deacetylases