title: Remodeling of nuclear landscapes during human myelopoietic cell differentiation maintains co-aligned active and inactive nuclear compartments.
abstract: BACKGROUND
  Previous studies of higher order chromatin organization in nuclei of mammalian species revealed both structural consistency and species-specific differences between cell lines and during early embryonic development. Here, we extended our studies to nuclear landscapes in the human myelopoietic lineage representing a somatic cell differentiation system. Our longterm goal is a search for structural features of nuclei, which are restricted to certain cell types/species, as compared to features, which are evolutionary highly conserved, arguing for their basic functional roles in nuclear organization.
  
  
  RESULTS
  Common human hematopoietic progenitors, myeloid precursor cells, differentiated monocytes and granulocytes analyzed by super-resolution fluorescence microscopy and electron microscopy revealed profound differences with respect to global chromatin arrangements, the nuclear space occupied by the interchromatin compartment and the distribution of nuclear pores. In contrast, we noted a consistent organization in all cell types with regard to two co-aligned networks, an active (ANC) and an inactive (INC) nuclear compartment delineated by functionally relevant hallmarks. The ANC is enriched in active RNA polymerase II, splicing speckles and histone signatures for transcriptionally competent chromatin (H3K4me3), whereas the INC carries marks for repressed chromatin (H3K9me3).
  
  
  CONCLUSIONS
  Our findings substantiate the conservation of the recently published ANC-INC network model of mammalian nuclear organization during human myelopoiesis irrespective of profound changes of the global nuclear architecture observed during this differentiation process. According to this model, two spatially co-aligned and functionally interacting active and inactive nuclear compartments (ANC and INC) pervade the nuclear space.
authors.affiliation: Department Biology II, Biocenter, Ludwig Maximilians University (LMU), Grosshadernerstr. 2, 82152 Martinsried, Germany ; School of Biological Sciences (SBS), Nanyang Technological University (NTU), Singapore, Singapore.
authors.forename: Barbara
authors.initials: B
authors.lastname: Hübner
authors.affiliation: Department of Life Sciences, University of Modena (Unimore), Modena, Italy.
authors.forename: Mariana
authors.initials: M
authors.lastname: Lomiento
authors.affiliation: Department of Life Sciences, University of Modena (Unimore), Modena, Italy.
authors.forename: Fabiana
authors.initials: F
authors.lastname: Mammoli
authors.affiliation: Department Biology II, Biocenter, Ludwig Maximilians University (LMU), Grosshadernerstr. 2, 82152 Martinsried, Germany ; Bundeswehr Institute of Radiobiology, Munich, Germany.
authors.forename: Doris
authors.initials: D
authors.lastname: Illner
authors.affiliation: Department Biology II, Biocenter, Ludwig Maximilians University (LMU), Grosshadernerstr. 2, 82152 Martinsried, Germany.
authors.forename: Yolanda
authors.initials: Y
authors.lastname: Markaki
authors.affiliation: Department of Life Sciences, University of Modena (Unimore), Modena, Italy.
authors.forename: Sergio
authors.initials: S
authors.lastname: Ferrari
authors.affiliation: Department Biology II, Biocenter, Ludwig Maximilians University (LMU), Grosshadernerstr. 2, 82152 Martinsried, Germany.
authors.forename: Marion
authors.initials: M
authors.lastname: Cremer
authors.affiliation: Department Biology II, Biocenter, Ludwig Maximilians University (LMU), Grosshadernerstr. 2, 82152 Martinsried, Germany.
authors.forename: Thomas
authors.initials: T
authors.lastname: Cremer
keywords: Active nuclear compartment; Chromatin density classification; Chromatin domain; Electron microscopy; Interchromatin compartment; Myelopoiesis; Nuclear architecture; Perichromatin region; Somatic cell differentiation; Super-resolution microscopy