title: LBR and lamin A/C sequentially tether peripheral heterochromatin and inversely regulate differentiation.
abstract: Eukaryotic cells have a layer of heterochromatin at the nuclear periphery. To investigate mechanisms regulating chromatin distribution, we analyzed heterochromatin organization in different tissues and species, including mice with mutations in the lamin B receptor (Lbr) and lamin A (Lmna) genes that encode nuclear envelope (NE) proteins. We identified LBR- and lamin-A/C-dependent mechanisms tethering heterochromatin to the NE. The two tethers are sequentially used during cellular differentiation and development: first the LBR- and then the lamin-A/C-dependent tether. The absence of both LBR and lamin A/C leads to loss of peripheral heterochromatin and an inverted architecture with heterochromatin localizing to the nuclear interior. Myoblast transcriptome analyses indicated that selective disruption of the LBR- or lamin-A-dependent heterochromatin tethers have opposite effects on muscle gene expression, either increasing or decreasing, respectively. These results show how changes in NE composition contribute to regulating heterochromatin positioning, gene expression, and cellular differentiation during development.
authors: Department of Biology II, Center for Integrated Protein Science Munich (CIPSM), Ludwig-Maximilians University Munich, Grosshadernerstrasse 2, 82152 Planegg-Martinsried, Germany.
authors: Irina
authors: I
authors: Solovei
authors: Audrey S
authors: AS
authors: Wang
authors: Katharina
authors: K
authors: Thanisch
authors: Christine S
authors: CS
authors: Schmidt
authors: Stefan
authors: S
authors: Krebs
authors: Monika
authors: M
authors: Zwerger
authors: Tatiana V
authors: TV
authors: Cohen
authors: Didier
authors: D
authors: Devys
authors: Roland
authors: R
authors: Foisner
authors: Leo
authors: L
authors: Peichl
authors: Harald
authors: H
authors: Herrmann
authors: Helmut
authors: H
authors: Blum
authors: Dieter
authors: D
authors: Engelkamp
authors: Colin L
authors: CL
authors: Stewart
authors: Heinrich
authors: H
authors: Leonhardt
authors: Boris
authors: B
authors: Joffe
mesh_terms: D000818:Animals; D020869:Gene Expression Profiling; D006570:Heterochromatin / Q000378:metabolism*; D034904:Lamin Type A / Q000378:metabolism*; D051379:Mice; D024510:Muscle Development; D032446:Myoblasts / Q000166:cytology / Q000378:metabolism*; D009685:Nuclear Envelope / Q000378:metabolism; D018160:Receptors, Cytoplasmic and Nuclear / Q000378:metabolism*; D000097682:Lamin B Receptor
chemical_list: D006570:Heterochromatin; D034904:Lamin Type A; D018160:Receptors, Cytoplasmic and Nuclear; D000097682:Lamin B Receptor; C440308:lamin C