title: LAP2zeta binds BAF and suppresses LAP2beta-mediated transcriptional repression.
abstract: Proteins of the nuclear envelope have been implicated as participating in gene silencing. BAF, a DNA- and LEM domain-binding protein, has been suggested to link chromatin to the nuclear envelope. We have previously shown that LAP2beta, a LEM-domain inner nuclear membrane protein, represses transcription through binding to HDAC3 and induction of histone H4 deacetylation. We now show that LAP2zeta, the smallest LAP2 family member, is also involved in regulation of transcription. We show that similar to other LEM-domain proteins LAP2zeta interacts with BAF. LAP2zeta-YFP and BAF co-localize in the cytoplasm, and overexpression of LAP2zeta leads to reduction of nucleoplasmic BAF. Mutations in the LAP2zeta-YFP LEM domain decrease its interaction with BAF retaining the nucleo-cytoplasmic distribution of BAF. Co-expression of LAP2beta and LAP2zeta results in inhibition of LAP2beta-induced gene silencing while overexpression of LAP2zeta alone leads to a small increase in transcriptional activity of various transcription factors. Our results suggest that LAP2zeta is a transcriptional regulator acting predominantly to inhibit LAP2beta-mediated repression. LAP2zeta may function by decreasing availability of BAF. These findings could have implications in the study of nuclear lamina-associated diseases and BAF-dependent retroviral integration.
authors.affiliation: Sheba Cancer Research Center and the Institute of Hematology, Chaim Sheba Medical Center, Tel-Hashomer, 52621, Israel.
authors.forename: Sigal
authors.initials: S
authors.lastname: Shaklai
authors.forename: Raz
authors.initials: R
authors.lastname: Somech
authors.forename: Einav Nili
authors.initials: EN
authors.lastname: Gal-Yam
authors.forename: Naamit
authors.initials: N
authors.lastname: Deshet-Unger
authors.forename: Sharon
authors.initials: S
authors.lastname: Moshitch-Moshkovitz
authors.forename: Koret
authors.initials: K
authors.lastname: Hirschberg
authors.forename: Ninette
authors.initials: N
authors.lastname: Amariglio
authors.forename: Amos J
authors.initials: AJ
authors.lastname: Simon
authors.forename: Gideon
authors.initials: G
authors.lastname: Rechavi
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D002467:Cell Nucleus / Q000378:metabolism; D003001:Cloning, Molecular; D003593:Cytoplasm / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D005786:Gene Expression Regulation; D006655:Histone Deacetylases / Q000378:metabolism; D006801:Humans; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D009687:Nuclear Proteins / Q000378:metabolism*; D020033:Protein Isoforms / Q000235:genetics / Q000378:metabolism; D012097:Repressor Proteins / Q000037:antagonists & inhibitors* / Q000378:metabolism*; D016415:Sequence Alignment; D015533:Transcriptional Activation; D000099186:Histone Deacetylase 3
chemical_list: D004268:DNA-Binding Proteins; D006655:Histone Deacetylases; D008565:Membrane Proteins; D009687:Nuclear Proteins; D020033:Protein Isoforms; D012097:Repressor Proteins; D000099186:Histone Deacetylase 3; C501959:BANF1 protein, human; C093413:lamina-associated polypeptide 2