Histone Acetyltransferase hALP and Nuclear Membrane Protein hsSUN1 Function in De-condensation of Mitotic Chromosomes

Abstract

Replicated mammalian chromosomes condense to segregate during anaphase, and they de-condense at the conclusion of mitosis. Currently, it is not understood what the factors and events are that specify de-condensation. Here, we demonstrate that chromosome de-condensation needs the function of an inner nuclear membrane (INM) protein hsSUN1 and a membrane-associated histone acetyltransferase (HAT), hALP. We propose that nascently reforming nuclear envelope employs hsSUN1 and hALP to acetylate histones for de-compacting DNA at the end of mitosis.The eukaryotic nucleus is separated from other organelles by an envelope containing two membrane layers continuous with the endoplasmic reticulum. Nuclear membrane proteins fall into three categories according to their localization. The first group is the trans-nuclear membrane proteins resident in the nuclear pore complex (NPC).2 The second group contains the inner membrane proteins (INM), which include the lamin B receptor (LBR), emerin, and lamin-associated polypeptides (LAPs). The third group includes proteins underlying the nuclear membrane such as nuclear lamina (1). Functionally, the INM provides a physical barrier; the NPC serves for the transport of material between the nucleus and the cytoplasm (2); and the nuclear lamina erects a meshwork, which maintains nuclear structure and assists indirectly in DNA replication and RNA processing (3, 4).Most INM proteins are associated with the nuclear lamina. In a proteomic study of INM proteins, in addition to 13 known proteins, 67 uncharacterized open reading frames (ORFs) were identified (5

Requirement for Sun1 in the expression of meiotic reproductive genes and piRNA

“…The N terminus of Sun1 is required for its inner nuclear membrane localization (Chi et al, 2007;Liu et al, 2007), while the SUN C terminus connects to the cytoskeleton through nesprin (Padmakumar et al, 2005). To investigate the physiological function of mammalian Sun1, we generated a Sun1 knockout mouse by targeted deletion of exons 10 and 11 (amino acids 344 to 408) that correspond to the transmembrane domains.…”

“…Conversely, the Caenorhabditis elegans SUNdomain protein Unc-84 is required for nuclear migration and anchorage (Lee et al, 2002). In mammalian cells, the N terminus of Sun1 targets the protein to the inner nuclear membrane (Chi et al, 2007), while the C terminus of the protein connects to cytoplasmic actin through a direct interaction with Nesprin (Crisp et al, 2006;Padmakumar et al, 2005). In somatic cells, human SUN1 has been described to be one of the early INM factors that associate with segregated daughter chromosomes in anaphase, participating in post-mitotic chromatin de-condensation by recruiting a membraneassociated histone acetyl transferase, hALP (Chi et al, 2007).…”

SUN1 splice variants, SUN1_888, SUN1_785, and predominant SUN1_916, variably function in directional cell migration

“…[1][2][3][4] Mammalian SUN proteins are encoded by at least 5 genes, SUN1»5. SUN1 and SUN2 are widely expressed in mammalian somatic cells.…”

Nesprin 4 is an outer nuclear membrane protein that can induce kinesin-mediated cell polarization

“…Because these also interact with nuclear components, including A-type lamins (24,25,28), and a histone acetyl transferase [in the case of Sun1 (29)], Sun-nesprin pairs represent links in a molecular chain connecting the cytoskeleton to nuclear structures. We refer to these as LINC complexes (linker of the cytoskeleton and nucleoskeleton).…”