title: Barrier-to-Autointegration Factor influences specific histone modifications.
abstract: Defects in the nuclear envelope or nuclear 'lamina' networks cause disease and can perturb histone posttranslational (epigenetic) regulation. Barrier-to-Autointegration Factor (BAF) is an essential but enigmatic lamina component that binds lamins, LEM-domain proteins, DNA and histone H3 directly. We report that BAF copurified with nuclease-digested mononucleosomes and associated with modified histones in vivo. BAF overexpression significantly reduced global histone H3 acetylation by 18%. In cells that stably overexpressed BAF 3-fold, silencing mark H3-K27-Me1/3 and active marks H4-K16-Ac and H4-Ac5 decreased significantly. Significant increases were also seen for silencing mark H3-K9-Me3, active marks H3-K4-Me2, H3-K9/K14-Ac and H4-K5-Ac and a mark (H3-K79-Me2) associated with both active and silent chromatin. Other increases (H3-S10-P, H3-S28-P and silencing mark H3-K9-Me2) did not reach statistical significance. BAF overexpression also significantly influenced cell cycle distribution. Moreover, BAF associated in vivo with SET/I2PP2A (protein phosphatase 2A inhibitor; blocks H3 dephosphorylation) and G9a (H3-K9 methyltransferase), but showed no detectable association with HDAC1 or HATs. These findings reveal BAF as a novel epigenetic regulator and are discussed in relation to BAF deficiency phenotypes, which include a hereditary progeria syndrome and loss of pluripotency in embryonic stem cells.
authors: Department of Cell Biology, The Johns Hopkins University School of Medicine, Baltimore, MD, USA.
authors: Rocío
authors: R
authors: Montes de Oca
authors: Paul R
authors: PR
authors: Andreassen
authors: Katherine L
authors: KL
authors: Wilson
mesh_terms: D000107:Acetylation; D000818:Animals; D002453:Cell Cycle; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D044127:Epigenesis, Genetic; D006367:HeLa Cells; D056488:Histone Chaperones / Q000235:genetics / Q000378:metabolism; D056284:Histone Deacetylase 1 / Q000235:genetics / Q000378:metabolism; D006657:Histones / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D034882:Lamins / Q000235:genetics / Q000378:metabolism; D034881:Nuclear Lamina / Q000235:genetics / Q000378:metabolism*; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*; D011371:Progeria / Q000235:genetics / Q000378:metabolism*; D011499:Protein Processing, Post-Translational; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D014982:Xenopus laevis
chemical_list: C501959:BANF1 protein, human; D004268:DNA-Binding Proteins; D056488:Histone Chaperones; D006657:Histones; D034882:Lamins; D009687:Nuclear Proteins; C513473:SET protein, human; D014157:Transcription Factors; C110550:HDAC1 protein, human; D056284:Histone Deacetylase 1