Nuclear envelope-limited chromatin sheets (ELCS) and heterochromatin higher order structure

Abstract

The interphase nucleus and nuclear envelope can acquire a myriad of shapes in normal or pathological cell states. There exist a wide variety of indentations and invaginations, of protrusions and evaginations. It has been difficult to classify and name all of these nuclear shapes and, consequently, a barrier to understanding the biochemical and biophysical causes. This review focuses upon one type of nuclear envelope shape change, named "nuclear envelope-limited chromatin sheets" (ELCS), which appears to involve exaggerated nuclear envelope growth, carrying with it one or more layers of approximately 30 nm diameter heterochromatin. A hypothesis on the formation of ELCS is proposed, relating higher order heterochromatin structure in an interphase nucleus, nuclear envelope growth, and nuclear envelope-heterochromatin interactions.

An epichromatin epitope: Persistence in the cell cycle and conservation in evolution

“…7) clearly demonstrates the presence of the epichromatin epitope within the condensed heterochromatic region adjacent to the nuclear envelope, as well as within the single heterochromatic layer of ELCS. 5 These images prove that the epichromatin epitope does include peripheral heterochromatin. However, it is becoming increasingly clear that some transcriptionally-active euchromatin can be localized near the nuclear envelope.…”

“…Describing these principles is a major goal of cell biology and encompasses understanding the interphase nucleus, the mitotic chromosome and other chromatin structural states. [1][2][3][4][5] A major advance in our understanding of the organization of chromatin came with the description of chromosome territories (CTs), 6,7 which demonstrated that the individuality of mitotic chromosomes is preserved, albeit in a swollen form, within the interphase nucleus. Evidence has also been presented that within these territories chromatin exists in "knot-free" globules, analogous to the nucleosomal "beads-on-a-string"; but at…”

“…This differentiation process takes 3-4 days in the subline HL-60/S4, leading to nuclear lobulation and formation of extensive sheets containing a single layer of ~30 nm chromatin fibers sandwiched between apposed nuclear envelopes. 5,30 These envelope-limited chromatin sheets (ELCS) are an extension of the adjacent NE membranes, with the ~30 nm chromatin layer in ELCS continuous to the most peripheral chromatin layer in the adjacent nuclear lobule. Employing pre-embedded thin section immunoelectron microscopy with a gold-labeled secondary antibody, the presence of the epichromatin epitope can be clearly visualized (Fig.…”

Lamin B receptor

“…53,70,71 However, there must be functional redundancy, since homozygous ic EPRO cells are deficient in LBR but can still divide (and differentiate) in vitro. 85,87 Our speculation that LBR is involved with NE membrane growth is based upon our studies with granulocytic cells differentiation in vitro and in vivo: (1) a positive correlation was observed between increased LBR levels in HL-60 cells, appearance of nuclear lobulation and formation of ELCS; 81,82,89 (2) a or intranuclear membranes. High levels of expression of GFP-lamins (not including lamin C) lead to extensive intranuclear membranes.…”

“…88 In the absence of sufficient LBR, the differentiated granulocyte nuclei are ovoid, appear to have a reduced NE surface area, and the heterochromatin redistributes towards the center of the nucleus. [84][85][86] In vitro granulopoiesis of the human acute myeloid leukemia cells (HL-60) with retinoic acid results in a marked increase of LBR content and nuclear lobulation with an exaggerated growth of the NE into sheets (nuclear envelope-limited chromatin sheets, or "ELCS" 81,89 ). It should also be mentioned that overexpression of the C-terminal region of LBR following transfection of HeLa cells results in perinuclear aggregates, stacks of overproduced membranes pinched off the NE, 51 which are devoid of lamin B.…”