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Burke B.,Singapore Institute of Medical Biology
Cell | Year: 2012

LINC complexes are structures embedded within the nuclear envelope that mechanically couple the nucleus and cytoskeleton. They consist of SUN domain proteins of the inner nuclear membrane associated with KASH domain proteins in the outer nuclear membrane. Atomic resolution structures of SUN-KASH pairs now provide new insight in to the mechanisms of LINC complex assembly. © 2012 Elsevier Inc.

Horn H.F.,Singapore Institute of Medical Biology
Current Topics in Developmental Biology | Year: 2014

The LINC complex spans the nuclear envelope and plays critical roles in coordinating nuclear and cytoplasmic activities and in organizing nuclear and cytoskeletal features. LINC complexes are assembled from KASH and SUN-domain proteins, which interact in the nuclear envelope and form a physical link between the cytoskeleton and the nuclear interior. A number of diseases have been associated with mutations in genes coding for LINC complex proteins. Mouse models of LINC complex protein have provided valuable insight into LINC complex functions and into how these proteins contribute to the various diseases with which they have been associated. © 2014 Elsevier Inc.

Burke B.,Singapore Institute of Medical Biology | Doye V.,University Paris Diderot
Cellular and Molecular Life Sciences | Year: 2010

The trafficking of macromolecules between the cytoplasm and the nucleus is controlled by the nuclear pore complexes (NPCs) and various transport factors that facilitate the movement of cargos through the NPCs and their accumulation in the target compartment. While their functions in transport are well established, an ever-growing number of observations have also linked components of the nuclear transport machinery to processes that control chromosome segregation during mitosis, including spindle assembly, kinetochore function, and the spindle assembly checkpoint. In this review, we will discuss this evolving area of study and emerging hypotheses that propose key roles for components of the nuclear transport apparatus in mitotic progression. © Springer Basel AG 2010.

Lo K.A.,Singapore Institute of Medical Biology
Bioscience reports | Year: 2013

Adipose tissue has a central role in the regulation of energy balance and homoeostasis. There are two main types of adipose tissue: WAT (white adipose tissue) and BAT (brown adipose tissue). WAT from certain depots, in response to appropriate stimuli, can undergo a process known as browning where it takes on characteristics of BAT, notably the induction of UCP1 (uncoupling protein 1) expression and the presence of multilocular lipid droplets and multiple mitochondria. How browning is regulated is an intense topic of investigation as it has the potential to tilt the energy balance from storage to expenditure, a strategy that holds promise to combat the growing epidemic of obesity and metabolic syndrome. This review focuses on the transcriptional regulators as well as various proteins and secreted mediators that have been shown to play a role in browning. Emphasis is on describing how many of these factors exert their effects by regulating the three main transcriptional regulators of classical BAT development, namely PRDM16 (PR domain containing 16), PPARγ (peroxisome proliferator-activated receptor γ) and PGC-1α (peroxisome proliferator-activated receptor γ coactivator 1α), which have been shown to be the key nodes in the regulation of inducible brown fat.

Messerschmidt D.M.,Agency for Science, Technology and Research Singapore | Knowles B.B.,The Jackson Laboratory | Knowles B.B.,Singapore Institute of Medical Biology | Solter D.,Singapore Institute of Medical Biology
Genes and Development | Year: 2014

Methylation of DNA is an essential epigenetic control mechanism in mammals. During embryonic development, cells are directed toward their future lineages, and DNA methylation poses a fundamental epigenetic barrier that guides and restricts differentiation and prevents regression into an undifferentiated state. DNA methylation also plays an important role in sex chromosome dosage compensation, the repression of retrotransposons that threaten genome integrity, the maintenance of genome stability, and the coordinated expression of imprinted genes. However, DNA methylation marks must be globally removed to allow for sexual reproduction and the adoption of the specialized, hypomethylated epigenome of the primordial germ cell and the preimplantation embryo. Recent technological advances in genome-wide DNA methylation analysis and the functional description of novel enzymatic DNA demethylation pathways have provided significant insights into the molecular processes that prepare the mammalian embryo for normal development. © 2014 Messerschmidt et al.

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