Lipid raft dynamics linked to sperm competency for fertilization in mice
It is well known that mammalian sperm acquires fertilization ability after several maturation processes, particularly within the female reproductive tract. In a previous study, we found that both glycosylphosphatidylinositol (GPI)‐anchored protein (GPI‐AP) release and lipid raft movement occur during the sperm maturation process. In several genetic studies, release of GPI‐AP is a crucial step for sperm fertilization ability in the mouse. Here, we show that lipid raft movement is also fundamental for sperm to be competent for fertilization by comparing the sperm maturation process of two mouse inbred strains, C57BL/6 ...
Source: Genes to Cells - April 1, 2017 Category: Genetics & Stem Cells Authors: Hitomi Watanabe, Rie Takeda, Keiji Hirota, Gen Kondoh Tags: Brief Report Source Type: research

Aging ‐dependent expression of synapse‐related proteins in the mouse brain
A synapse is a cell adhesion structure that permits a neuron to pass a chemical or electrical signal to another neuron. They connect neurons and form neural networks that are essential for brain functions, such as learning and memory. At a chemical synapse, the presynapse and the postsynapse are connected by cell adhesion molecules. The presynapse contains synaptic vesicles and their release machinery, whereas the postsynapse contains postsynaptic densities and receptors for the neurotransmitters. Many proteins constituting a synapse have been identified, but their life‐span expression profiles remain elusive. Here, we i...
Source: Genes to Cells - April 1, 2017 Category: Genetics & Stem Cells Authors: Hajime Shiotani, Tomohiko Maruo, Shotaro Sakakibara, Muneaki Miyata, Kenji Mandai, Hideki Mochizuki, Yoshimi Takai Tags: Original Article Source Type: research

Thymine DNA glycosylase modulates DNA damage response and gene expression by base excision repair ‐dependent and independent mechanisms
Thymine DNA glycosylase (TDG) is a base excision repair (BER) enzyme, which is implicated in correction of deamination‐induced DNA mismatches, the DNA demethylation process and regulation of gene expression. Because of these pivotal roles associated, it is crucial to elucidate how the TDG functions are appropriately regulated in vivo. Here, we present evidence that the TDG protein undergoes degradation upon various types of DNA damage, including ultraviolet light (UV). The UV‐induced degradation of TDG was dependent on proficiency in nucleotide excision repair and on CRL4CDT2‐mediated ubiquitination that requires a ...
Source: Genes to Cells - March 19, 2017 Category: Genetics & Stem Cells Authors: Tomohumi Nakamura, Kouichi Murakami, Haruto Tada, Yoshihiko Uehara, Jumpei Nogami, Kazumitsu Maehara, Yasuyuki Ohkawa, Hisato Saitoh, Hideo Nishitani, Tetsuya Ono, Ryotaro Nishi, Masayuki Yokoi, Wataru Sakai, Kaoru Sugasawa Tags: Original Article Source Type: research

Corrigendum
(Source: Genes to Cells)
Source: Genes to Cells - March 13, 2017 Category: Genetics & Stem Cells Tags: Corrigendum Source Type: research

Issue Information
Front cover: We found a spray of ume (Japanese apricot) with some pretty blossoms. To bring out the best appearance of the blossoms, we arranged it in front of a plate on which a budding yeast strain had been streaked. Since the strain had ade2 mutation and carried a plasmid containing ADE2 gene, a moderate number of colonies turned into deep pink color due to loss of the plasmid were scattered on the medium. What we found as a result was a perfect picture of ume blossoms illuminated from behind by the rising full moon. Designed by TRAIS Co., Ltd. (Kobe, Japan) (Source: Genes to Cells)
Source: Genes to Cells - March 13, 2017 Category: Genetics & Stem Cells Tags: Issue Information Source Type: research

3D structural analysis of protein O ‐mannosyl kinase, POMK, a causative gene product of dystroglycanopathy
Orchestration of the multiple enzymes engaged in O‐mannose glycan synthesis provides a matriglycan on α‐dystroglycan (α‐DG) which attracts extracellular matrix (ECM) proteins such as laminin. Aberrant O‐mannosylation of α‐DG leads to severe congenital muscular dystrophies due to detachment of ECM proteins from the basal membrane. Phosphorylation at C6‐position of O‐mannose catalyzed by protein O‐mannosyl kinase (POMK) is a crucial step in the biosynthetic pathway of O‐mannose glycan. Several mis‐sense mutations of the POMK catalytic domain are known to cause a severe congenital muscular dystrophy, Wa...
Source: Genes to Cells - March 1, 2017 Category: Genetics & Stem Cells Authors: Masamichi Nagae, Sushil K. Mishra, Makiko Neyazaki, Rika Oi, Akemi Ikeda, Naohiro Matsugaki, Satoko Akashi, Hiroshi Manya, Mamoru Mizuno, Hirokazu Yagi, Koichi Kato, Toshiya Senda, Tamao Endo, Terukazu Nogi, Yoshiki Yamaguchi Tags: Original Article Source Type: research

Behavioral and neuroanatomical analyses in a genetic mouse model of 2q13 duplication
In this study, we generated bacterial artificial chromosome‐based transgenic mice, called 2q13 dup, that recapitulate human chromosome 2q13 duplication and contain one extra copy of the Nphp1 transgene. To analyze any behavioral alterations in 2q13 dup mice, we conducted a battery of behavioral tests. Although 2q13 dup mice show no significant differences in social behavior, they show deficits in spontaneous alternation behavior and fear memory. We also carried out magnetic resonance imaging to confirm whether copy number gain in this locus affects the neuroanatomy. There was a trend toward a decrease in the cerebellar p...
Source: Genes to Cells - March 1, 2017 Category: Genetics & Stem Cells Authors: Keiko Kishimoto, Jun Nomura, Jacob Ellegood, Keita Fukumoto, Jason P. Lerch, Daniel Moreno ‐De‐Luca, Thomas Bourgeron, Kota Tamada, Toru Takumi Tags: Original Article Source Type: research

HIV ‐1 susceptibility of transgenic rat‐derived primary macrophage/T cells and a T cell line that express human receptors, CyclinT1 and CRM1 genes
We developed transgenic (Tg) rats that express human CD4, CCR5, CXCR4, CyclinT1, and CRM1 genes. Tg rat macrophages were efficiently infected with HIV‐1 and supported production of infectious progeny virus. By contrast, both rat primary CD4+ T cells and established T cell lines expressing human CD4, CCR5, CyclinT1, and CRM1 genes were infected inefficiently, but this was ameliorated by inhibition of cyclophilin A. The infectivity of rat T cell‐derived virus was lower than that of human T cell‐derived virus. Tg rats that express human CD4, CCR5, CXCR4, CycT1, and CRM1 were created. Tg rat macrophages support propagat...
Source: Genes to Cells - March 1, 2017 Category: Genetics & Stem Cells Authors: Hisatoshi Shida, Hiroyuki Okada, Hajime Suzuki, Xianfeng Zhang, Jing Chen, Yasuko Tsunetsugu ‐Yokota, Yuetsu Tanaka, Fumika Yakushiji, Yoshio Hayashi Tags: Original Article Source Type: research

Chromatin tethering to the nuclear envelope by nuclear actin filaments: a novel role of the actin cytoskeleton in the Xenopus blastula
The Xenopus oocyte is known to accumulate filamentous or F‐actin in the nucleus, but it is currently unknown whether F‐actin also accumulates in embryo nuclei. Using fluorescence‐labeled actin reporters, we examined the actin distribution in Xenopus embryonic cells and found that F‐actin accumulates in nuclei during the blastula stage but not during the gastrula stage. To further investigate nuclear F‐actin, we devised a Xenopus egg extract that reproduces the formation of nuclei in which F‐actin accumulates. Using this extract, we found that F‐actin accumulates primarily at the subnuclear membranous region a...
Source: Genes to Cells - February 28, 2017 Category: Genetics & Stem Cells Authors: Haruka Oda, Natsuki Shirai, Naoko Ura, Keita Ohsumi, Mari Iwabuchi Tags: Original Article Source Type: research

Dickkopf 3 attenuates xanthine dehydrogenase expression to prevent oxidative stress ‐induced apoptosis
Dickkopf (DKK) 3 is a DKK glycoprotein family member that controls cell fate during embryogenesis and exerts opposing effects on survival in a cell type‐dependent manner; however, the mechanisms governing its pro‐apoptosis versus pro‐survival functions remain unclear. Here, we investigated DKK3 function in Li21 hepatoma cells and tPH5CH immortalized hepatocytes. DKK3 knockdown by siRNA resulted in reactive oxygen species accumulation and subsequent apoptosis, which were abrogated by administration of the antioxidant N‐acetyl‐cysteine. Moreover, forced DKK3 over‐expression induced resistance to hydrogen peroxide...
Source: Genes to Cells - February 28, 2017 Category: Genetics & Stem Cells Authors: Shuang Qui, Junko Kano, Masayuki Noguchi Tags: Original Article Source Type: research

Geminin is an indispensable inhibitor of Cdt1 in mouse embryonic stem cells
Geminin is implicated in regulation of the cell cycle and differentiation. Although loss of Geminin triggers unscheduled DNA rereplication as a result of interruption of its interaction with Cdt1 in some somatic cancer cells, whether such cell cycle regulation also operates in embryonic stem cells (ESCs) has remained unclear. To characterize the Geminin‐Cdt1 axis in ESCs and compare it with that in somatic cells, we established conditional knockout (KO) of Geminin in mouse ESCs and mouse embryonic fibroblasts (MEFs). Geminin KO ESCs manifest a large flattened morphology, develop polyploidy accompanied by DNA damage and G...
Source: Genes to Cells - February 28, 2017 Category: Genetics & Stem Cells Authors: Masaki Hosogane, Lena Bosu, Emiko Fukumoto, Hidetoshi Yamada, Soichiro Sato, Keiko Nakayama Tags: Original Article Source Type: research

Ric ‐8A, an activator protein of Gαi, controls mammalian epithelial cell polarity for tight junction assembly and cystogenesis
Correct cyst morphogenesis of epithelial cells requires apical–basal polarization, which is partly regulated by mitotic spindle orientation, a process dependent on the heterotrimeric G protein subunit Gαi and its binding protein LGN. Here, we show that in three‐dimensional culture of mammalian epithelial Madin–Darby canine kidney (MDCK) cells, the Gαi‐activating protein Ric‐8A is crucial for orientation of the mitotic spindle and formation of normal cysts that comprise a single layer of polarized cells with their apical surfaces lining an inner lumen. Consistent with the involvement of LGN, cystogenesis can be ...
Source: Genes to Cells - February 9, 2017 Category: Genetics & Stem Cells Authors: Kanako Chishiki, Sachiko Kamakura, Junya Hayase, Hideki Sumimoto Tags: Original Article Source Type: research

Issue Information
Front cover: Walking monozygotic twin sisters in the snow are sharing an umbrella. They share the same genotype; however, they seem to have a different personality and taste as their kimono. It has been pointed out that the difference in epigenome would cause such difference in personality. The data printed on their sleeves that was obtained with the bisulfite sequencing (a method that can detect methylation of individual cytosine residues in DNA) and is showing their methylation patterns at a certain locus of the genome suggests that there are epigenetic differences between them. Our knowledge of the relationship between ...
Source: Genes to Cells - February 6, 2017 Category: Genetics & Stem Cells Tags: Issue Information Source Type: research

Histone H1 chaperone activity of TAF ‐I is regulated by its subtype‐dependent intramolecular interaction
Linker histone H1 is involved in the regulation of gene activity through the maintenance of higher‐order chromatin structure. Previously, we have shown that template activating factor‐I (TAF‐I or protein SET) is involved in linker histone H1 dynamics as a histone H1 chaperone. In human and murine cells, two TAF‐I subtypes exist, namely TAF‐Iα and TAF‐Iβ. TAF‐I has a highly acidic amino acid cluster in its C‐terminal region and forms homo‐ or heterodimers through its dimerization domain. Both dimer formation and the C‐terminal region of TAF‐I are essential for the histone chaperone activity. TAF‐I...
Source: Genes to Cells - January 31, 2017 Category: Genetics & Stem Cells Authors: Kaori Kajitani, Kohsuke Kato, Kyosuke Nagata Tags: Original Article Source Type: research

Xeroderma pigmentosum group C protein interacts with histones: regulation by acetylated states of histone H3
In the mammalian global genome nucleotide excision repair pathway, two damage recognition factors, XPC and UV‐DDB, play pivotal roles in the initiation of the repair reaction. However, the molecular mechanisms underlying regulation of the lesion recognition process in the context of chromatin structures remain to be understood. Here, we show evidence that damage recognition factors tend to associate with chromatin regions devoid of certain types of acetylated histones. Treatment of cells with histone deacetylase inhibitors retarded recruitment of XPC to sites of UV‐induced DNA damage and the subsequent repair process. ...
Source: Genes to Cells - January 31, 2017 Category: Genetics & Stem Cells Authors: Erina Kakumu, Seiya Nakanishi, Hiromi M. Shiratori, Akari Kato, Wataru Kobayashi, Shinichi Machida, Takeshi Yasuda, Naoko Adachi, Naoaki Saito, Tsuyoshi Ikura, Hitoshi Kurumizaka, Hiroshi Kimura, Masayuki Yokoi, Wataru Sakai, Kaoru Sugasawa Tags: Original Article Source Type: research