Table of Contents

Volume 3, Issue 2

  March 1, 2012

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LANDES HIGHLIGHTS

Landes Highlights

Eva Riedmann
http://dx.doi.org/10.4161/nucl.19773
PDF




MEMOIR

Open Access Article

“Tall oaks fallen”: Three Pioneers of Chromosome Science

Thoru Pederson
http://dx.doi.org/10.4161/nucl.19714
Abstract | PDF

“As when, upon a tranced summer-night,
Those green-robed senators of mighty woods,
Tall oaks, branch-charmed by the earnest stars,
Dream, and so dream all night without a stir.”
 
                                                     William Butler Yeats
 
 
 
The past 12 months saw the loss of three “tall oaks”—pioneers in the molecular and cell biology of chromosomes:  David Prescott, Paul Doty and Oscar Miller. Here I offer remembrances of each of them, not as definitive memoirs but simply with the goal of informing the next generation about pioneers whose names they may hardly know today.





COMMENTARIES

The liquid drop nature of nucleoli

John F. Marko
http://dx.doi.org/10.4161/nucl.19099
Abstract | PDF

Nucleoli are prominent subnuclear organelles, and are known to be hubs of ribosome synthesis. A recent study of Brangwynne et al. reports that the nucleoli of Xenopus oocytes display “liquid drop” behavior, suggesting that nucleolar structure may be driven by rather simple physical principles.

Hox in space: Gene cluster regulation linked to folding of chromatin

Alexey V. Pindyurin and Bas van Steensel
http://dx.doi.org/10.4161/nucl.19159
Abstract | Full Text | PDF

The spatial folding of chromatin has been proposed to be involved in the regulation and coordination of gene expression. The mammalian Hox gene clusters form a particularly interesting case of coordinated gene regulation. Within each Hox cluster, the linear order of the genes closely reflects their temporal and anatomical expression pattern. This striking phenomenon suggests that the overall structure of the Hox clusters is important for their regulation. Recent studies employing chromatin conformation capture techniques indicate that Hox clusters adopt a remarkable spatial configuration, in which active and inactive genes are segregated into two distinct chromatin compartments. Here we discuss the possible underlying mechanisms and regulatory roles of this spatial compartmentalization.




MEETING REPORT

Nucleo-cytoplasmic actin relationships in Stockholm

Maria K. Vartiainen
http://dx.doi.org/10.4161/nucl.19515
Abstract | PDF

The Wenner-Gren Foundations symposium “Actin and Actin-associated Proteins from Genes to Polysomes” took place at the Wenner-Gren Center in Stockholm, Sweden, on September 7-10th, 2011. As the name of the symposium implied, the organizing committee, consisting of local organizers Piergiorgio Percipalle, Neus Visa and Ann Kristin Östlund Farrants from Stockholm and Thoru Pederson from Worcester, USA, had boldly decided to embrace the unconventional roles of actin, namely its connections to the gene expression apparatus all the way from the nuclear genes to the cytoplasmic protein synthesis machineries. The organizers assembled a respectable crowd of 25 speakers, with very diverse backgrounds, but a common interest in understanding how actin and its associated factors may function outside their conventional roles in the cytoskeleton. As many people presented unpublished work, I will not go into detail of these talks but will rather aim to highlight the discussed topics and their possible implications to this exciting research field.




EXTRA VIEWS

Chromatin signatures of active enhancers

Salvatore Spicuglia and Laurent Vanhille
http://dx.doi.org/10.4161/nucl.19232
Abstract | Full Text | PDF

Gene-distal cis-regulatory sequences, such as enhancers, are key contributors of tissue-specific gene expression. In particular, enhancers can be located up to hundreds of kilobases from the promoters that they control, making their identification challenging. Thanks to the recent technological advances to map histone modifications and chromatin-associated factors genome-wide, several studies have begun to characterize chromatin signatures of active enhancers. Here, we discuss some of these results and how they provide new insights into the tissue-specific organization of enhancer repertoires.

CRM1 plays a nuclear role in transporting snoRNPs to nucleoli in higher eukaryotes

Celine Verheggen and Edouard Bertrand
http://dx.doi.org/10.4161/nucl.19266
Abstract | PDF

Here, we review the sn- and snoRNA transport pathways in S. Cerevisiae and humans, aiming at understanding how they evolved and how common factors can have distinct functions depending on the RNA they bind. We give a particular emphasis on Tgs1, the cap hypermethylase that is conserved from yeast to humans and appears to play a central role in both sn- and snoRNA biogenesis. In yeast, Tgs1 hypermethylates sn- and snoRNAs in the nucleolus. In humans, Tgs1 occurs in two forms: a long isoform (Tgs1 LF), which locates in the cytoplasm and Cajal bodies, and which is predominantly associated with snRNAs; and a short isoform (Tgs1 SF), which is nuclear and mainly associates with snoRNAs. We show that Tgs1 LF is exported by CRM1 and that interaction with CRM1 competes for binding with the C-terminal domain of the core protein Nop58, which contains the Nucleolar localization signal of Box C/D snoRNPs (NoLS). Our data suggest a model where CRM1 removes Tgs1 LF from snoRNPs, thereby promoting nucleolar targeting via activation of their NoLS. In this review, we argue that CRM1, while first described as an export receptor, can also control the composition of nucleoplasmic complexes. Thus, it could coordinate the fate of these complexes with the general nucleo-cytoplasmic trafficking.

Repo-Man-PP1: A link between chromatin remodelling and nuclear envelope reassembly

Paola Vagnarelli and William C. Earnshaw
http://dx.doi.org/10.4161/nucl.19267
Abstract | PDF

Coordination of late mitotic events is crucial for the maintenance of genome stability and for the control of gene expression after cell division. Reversible protein phosphorylation regulates this process by de-phosphorylation of mitotic phospho-proteins in a sequential and coordinated manner: this allows an orderly sequence of events to take place during mitotic exit. We have identified Repo-Man/PP1 as a phosphatase complex that regulates temporally and spatially chromatin re-organization and nuclear envelope re-formation during anaphase-telophase.

 

 

 

Following CDK inactivation at anaphase onset, a pool of Repo-Man/PP1 localizes homogeneously to the anaphase chromatin, where it removes the major mitotic phosphorylations on Histone H3 (Thr3, Ser10 and Ser28). We have shown that this de-phosphorylation mediated by Repo-Man/PP1 is essential for the re-establishment of heterochromatin in post-mitotic cells.

A second pool of Repo-Man/PP1 targets to the periphery of chromosomes slightly later in anaphase. There, it contributes to the recruitment of Importin β to the chromatin. This fraction of Repo-Man appears to important in the regulation of nuclear pores and lamina re-assembly since depletion of the complex leads to an abnormal lamina morphology and nuclear shape in G1 cells.

In summary Repo-Man/PP1 represents a molecular coupler between chromatin re-modeling and nuclear envelope (NE) re-formation that coordinates these processes during mitotic exit.1

Fusing telomeres with RNF8

Jacqueline J.L. Jacobs
http://dx.doi.org/10.4161/nucl.19322
Abstract | Full Text | PDF

DNA repair activities at DNA double-strand breaks (DSBs) are under control of regulatory ubiquitylation events governed by the RNF8 and RNF168 ubiquitin-ligases. Defects in this regulatory mechanism, as with mutation of other key DNA damage-response factors, lead to genomic instability and cancer, presumably due to impaired repair of DNA lesions. Recent work revealed that RNF8 and RNF168 also play critical roles at natural chromosome ends, when no longer adequately shielded by telomeres. In contrast to repair of DSBs being needed to maintain genome integrity, repair activities at telomeres create chromosome end-to-end fusions that threaten genome integrity. Upon cell division these telomere fusions give rise to genomic alterations and instability via chromosomal missegregration and initiation of breakage-fusion-bridge cycles. Here I discuss the role of RNF8 at natural chromosome ends and its (potential) consequences.

Chromatin “pre-pattern” and epigenetic modulation in the cell fate choice of liver over pancreas in the endoderm

Cheng-Ran Xu and Kenneth Zaret
http://dx.doi.org/10.4161/nucl.19321
Abstract | Full Text | PDF

Understanding the basis for multipotency, whereby stem cells and other progenitors can differentiate into certain tissues and not others, provides insights into the mechanism of cell programming in development, homeostasis, and disease. We recently reported a screen of diverse chromatin marks to obtain clues about chromatin states in the multipotent embryonic endoderm. Genetic and pharmacologic tests of certain marks’ function demonstrated that the relevant chromatin modifying factors modulate the fate choice for liver or pancreas induction in the endoderm. The information about chromatin states from embryonic studies can be used to predict lineage-specific developmental potential and chromatin modifiers to enhance particular cell fate transitions from stem cells.

Transcriptional repression by the Msx1 homeoprotein is associated with global redistribution of the H3K27me3 repressive mark to the nuclear periphery

Jingqiang Wang and Cory Abate-Shen
http://dx.doi.org/10.4161/nucl.19477
Abstract | PDF

The spatial and temporal regulation of gene expression during development requires the concerted actions of sequence-specific transcriptional regulators and epigenetic chromatin modifiers, which are thought to function within precise nuclear compartments. However, coordination of these activities within the dynamic context of the nuclear environment is still largely unresolved. Here we discuss the implications of our recent work showing that transcriptional repression by the Msx1 homeoprotein is associated with global redistribution of the H3K27me3 repressive mark to the nuclear periphery during development.




REVIEW

Dynamics and diverse functions of nuclear pore complex proteins

Guillaume Chatel and Birthe Fahrenkrog
http://dx.doi.org/10.4161/nucl.19674
Abstract | PDF

Nuclear pore complexes (NPCs) are best known for their central role in controlling the molecular trafficking between the cytoplasm and the nucleus. NPCs are assembled from about 30 different proteins and a growing body of evidence suggests that these nucleoporins are not only acting in the context of NPCs, but also in the nucleoplasm and cytoplasm. In this context it is well accepted that a set of nucleoporins are important regulators of a variety of mitotic processes, including kinetochore assembly, spindle checkpoint control and cytokinesis, whereas others associate with chromatin and administer gene expression. However, the functional importance of nucleoporins go far beyond these roles and this review will provide an overview of the latest insights into the versatility of metazoan nucleoporins with an emphasis on their roles in cell migration, cellular signaling and tissue-specific activities.




RESEARCH PAPERS

Open Access Article

The nuclear envelope protein Nesprin-2 has roles in cell proliferation and differentiation during wound healing

R.N. Rashmi, Beate Eckes, Gernot Glöckner, Marco Groth, Sascha Neumann, Joachim Gloy, Lorenz Sellin, Gerd Walz, Maria Schneider, Iakowos Karakesisoglou, Ludwig Eichinger and Angelika A. Noegel
http://dx.doi.org/10.4161/nucl.19090
Abstract | Full Text | PDF

Nesprin-2, a type II transmembrane protein of the nuclear envelope, is a component of the LINC complex that connects the nuclear lamina with the actin cytoskeleton. To elucidate its physiological role we studied wound healing in Nesprin-2 Giant deficient mice and found that a loss of the protein affected wound healing particularly at later stages during fibroblast differentiation and keratinocyte proliferation leading to delayed wound closure. We identified altered expression and localization of transcription factors as one of the underlying mechanisms. Furthermore, the actin cytoskeleton which surrounds the nucleus was altered and keratinocyte migration was slowed down and focal adhesion formation enhanced. We also uncovered a new activity of Nesprin-2. When we probed for an interaction of Nesprin-2 Giant with chromatin we observed in ChIP Seq experiments an association of the protein with heterochromatic and centromeric DNA. Through this activity Nesprin-2 can affect the nuclear landscape and gene regulation. Our findings suggest functions for Nesprin-2 at the nuclear envelope (NE) in gene regulation and in regulation of the actin cytoskeleton which impact on wound healing.

Open Access Article

The nucleoporin ELYS/Mel28 regulates nuclear envelope subdomain formation in HeLa cells

Michaela Clever, Tomoko Funakoshi, Yasuhiro Mimura, Masatoshi Takagi and Naoko Imamoto
http://dx.doi.org/10.4161/nucl.19595
Abstract | PDF

In open mitosis, the nuclear envelope (NE) reassembles at the end of each mitosis. This process involves the reformation of the nuclear pore complex (NPC), the inner and outer nuclear membranes, and the nuclear lamina. In human cells, cell cycle-dependent NE subdomains exist, characterized as A-type lamin-rich/NPC-free or B-type lamin-rich/NPC-rich, which are initially formed as core or noncore regions on mitotic chromosomes, respectively. Although postmitotic NE formation has been extensively studied, little is known about the coordination of NPC and NE assembly. Here, we report that the nucleoporin ELYS/Mel28, which is crucial for postmitotic NPC formation, is essential for recruiting the lamin B receptor (LBR) to the chromosomal noncore region. Furthermore, ELYS/Mel28 is responsible for focusing of A-type lamin-binding proteins like emerin, Lap2α and the barrier-to-autointegration factor (BAF) at the chromosomal core region. ELYS/Mel28 biochemically interacts with the LBR in a phosphorylation-dependent manner. Recruitment of the LBR depends on the nucleoporin Nup107, which interacts with ELYS/Mel28, but not on nucleoporin Pom121, suggesting that the specific molecular interactions with ELYS/Mel28 are involved in the NE assembly at the noncore region. The depletion of the LBR affected neither the behavior of emerin nor Lap2α indicating that the recruitment of the LBR to mitotic chromosomes is not involved in formation of the core region. The depletion of ELYS/Mel28 also accelerates the entry into cytokinesis after recruitment of emerin to chromosomes. Our data show, that ELYS/Mel28 plays a role in NE subdomain formation in late mitosis.

Open Access Article

Phosphatidylserine colocalizes with epichromatin in interphase nuclei and mitotic chromosomes

Igor Prudovsky, Calvin Vary, Yolanda Markaki, Ada L. Olins and Donald Olins
http://dx.doi.org/10.4161/nucl.19662
Abstract | Full Text | PDF

Cycling eukaryotic cells rapidly re-establish the nuclear envelope and internal architecture following mitosis. Studies with a specific anti-nucleosome antibody recently demonstrated that the surface (“epichromatin”) of interphase and mitotic chromatin possesses a unique and conserved conformation, suggesting a role in postmitotic nuclear reformation. Here we present evidence showing that the anionic glycerophospholipid phosphatidylserine is specifically located in epichromatin throughout the cell cycle and is associated with nucleosome core histones. This suggests that chromatin bound phosphatidylserine may function as a nucleation site for the binding of ER and re-establishment of the nuclear envelope.