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101.
Regulated recruitment of HP1 to a euchromatic gene induces mitotically heritable,epigenetic gene silencing: a mammalian cell culture model of gene variegation 总被引:18,自引:2,他引:18
Ayyanathan K Lechner MS Bell P Maul GG Schultz DC Yamada Y Tanaka K Torigoe K Rauscher FJ 《Genes & development》2003,17(15):1855-1869
Heterochromatin protein 1 (HP1) is a key component of constitutive heterochromatin in Drosophila and is required for stable epigenetic gene silencing classically observed as position effect variegation. Less is known of the family of mammalian HP1 proteins, which may be euchromatic, targeted to expressed loci by repressor-corepressor complexes, and retained there by Lys 9-methylated histone H3 (H3-MeK9). To characterize the physical properties of euchromatic loci bound by HP1, we developed a strategy for regulated recruitment of HP1 to an expressed transgene in mammalian cells by using a synthetic, hormone-regulated KRAB repression domain. We show that its obligate corepressor, KAP1, can coordinate all the machinery required for stable gene silencing. In the presence of hormone, the transgene is rapidly silenced, spatially recruited to HP1-rich nuclear regions, assumes a compact chromatin structure, and is physically associated with KAP1, HP1, and the H3 Lys 9-specific methyltransferase, SETDB1, over a highly localized region centered around the promoter. Remarkably, silencing established by a short pulse of hormone is stably maintained for >50 population doublings in the absence of hormone in clonal-cell populations, and the silent transgenes in these clones show promoter hypermethylation. Thus, like variegation in Drosophila, recruitment of mammalian HP1 to a euchromatic promoter can establish a silenced state that is epigenetically heritable. 相似文献
102.
Ryoki Ishikawa Tsuyoshi Okagaki Kazuhiro Kohama 《Journal of muscle research and cell motility》1992,13(3):321-328
Summary From the plasmodia of a lower eukaryote,Physarum polycephalum, we have previously purified a 210-kDa protein that showed similar properties to those of smooth muscle caldesmon. Further characterization of the 210-kDa protein revealed that it bundled actin filaments. This bundling activity was inhibited by calmodulin in the presence of Ca2+. Unlike smooth muscle caldesmon, the 210-kDa protein bundled actin filaments whether or not a reducing agent, such as dithiothreitol, was present. The protein was shown to have two (or more) different actin-binding sites which were classified into salt-sensitive and salt-insensitive sites. Electron microscopy revealed that the 210-kDa protein was an elongated molecule (mean length, 97 ± 25 nm) which was bent in the middle. The Stokes radius and sedimentation coefficient of the 210-kDa protein were 130 Å and 2.9 S, respectively. An immunofluorescence study revealed that the 210-kDa protein colocalized with the bundles of actin filaments in thin-spread preparations ofPhysarum plasmodia, suggesting that the 210-kDa protein was regulating the appearance and disappearance of the actin bundles that are associated with the contraction-relaxation cycle of the plasmodia. 相似文献
103.
Expression cloning of gamma interferon-inducing antigens of Mycobacterium avium subsp. paratuberculosis 下载免费PDF全文
Three recombinant proteins, Map10, Map39, and Map41, produced based on nucleotide sequences obtained from the screening of Mycobacterium avium subsp. paratuberculosis genomic library expressed in Escherichia coli significantly elicited gamma interferon production in peripheral blood mononuclear cells from infected cattle. Two of these proteins were members of the PPE protein family. 相似文献
104.
Yuji Okuyama Mitsuhiko Yamada Chikako Kondo Eisaku Satoh Shojiro Isomoto Takashi Shindo Yoshiyuki Horio Masafumi Kitakaze Masatsugu Hori Y. Kurachi 《Pflügers Archiv : European journal of physiology》1998,435(5):595-603
The effects of potassium channel opening drugs and intracellular nucleotides on the ATP-sensitive K+ (KATP) channel composed of SUR2A and Kir6.2 in HEK293T cells were examined using the patch-clamp technique. The SUR2A/Kir6.2 channel
was activated effectively by pinacidil, marginally by nicorandil but not by diazoxide. The pinacidil-activated channel currents
were inhibited by glibenclamide with a K
i value of 160 nM. Upon formation of inside-out (I-O) patches, spontaneous openings of the channels appeared, which were inhibited
by intracellular ATP (ATPi) equipotently in the presence and in the absence of intracellular Mg2+ (Mg2+
i). The channel activity ran-down gradually in I-O patches. The run-down channels could be reactivated by ATPi only in the presence of Mg2+
i. Uridine 5’-diphosphate (UDP) antagonized the ATPi-mediated inhibition of the channel activity before run-down. After run-down, UDP activated the channel without antagonizing
ATPi-mediated channel inhibition. Thus, the SUR2A/Kir6.2 reproduced the major properties of the native cardiac KATP channel well in terms of nucleotide regulation and pharmacology, and therefore can be a useful tool with which to elucidate
the molecular mechanisms characterizing the KATP channel.
Received: 24 October 1997 / Received after revision and accepted: 4 December 1997 相似文献
105.
Masaharu Muranaka Shuji Suzuki Kazuhiro Koizumi Hiroshi Igarashi Hiroshi Okumura Koyo Takeda Kenji Tadokoro Yoshihiko Horiuchi 《The Journal of allergy and clinical immunology》1978,62(5):276-282
All of the five commercially available benzylpenicillin preparations obtained from different sources and a PcG preparation prepared by filtration of a commercial PcG on Sephadex G10 elicited the systemic anaphylactic reactions in guinea pigs which had been immunized with benzylpenicilloyl (BPO)-Ascaris extract conjugate (BPO-As) mixed with aluminum hydroxide gel. These preparations could evoke no such reactions in guinea pigs immunized with BPO-bovine gamma globulin conjugate (BPO-BGG) emulsified with complete Freund's adjuvant. The severity of the systemic anaphylactic reactions correlated significantly with the titers of either 8-day passive cutaneous anaphylactic (8-day PCA) reactions or 4-hr PCA reactions evoked with the same benzylpenicillin preparations. In vitro benzylpenicillin preparation contracted the tracheas of the guinea pigs immunized with BPO-As. These results indicated that the commercially available benzylpenicillin preparations have enough antigenicity to evoke systemic anaphylactic reactions in guinea pigs immunized with BPO-As mixed with aluminum hydroxide gel. Such guinea pigs represent an animal model for investigation of penicillin allergy. 相似文献
106.
Summary The effects of ambient and hypothalamic temperatures were studied on the hyperthermic responses to prostaglandins E1 and E2 (PGE1 and PGE2) injected intraventricularly in the unanesthetized rabbit. Hyperthermic responses to PGE1 observed at different thermal environments were approximately equal in magnitude and time course. However, the prevailing ambient temperature influenced the thermoregulatory mechanisms by which the hyperthermia was achieved. In a hot environment, PGE1-hyperthermia was brought about by suppression of heat loss mechanism with little change in heat production. During cold exposure body temperature was raised mainly by an increase in heat production without a significant change in heat loss. PGEs-hyperthermias were attenuated by warming and enhanced by cooling the anterior hypothalamus. These changes in the hyperthermic responses to PGE1 and PGE2 are in contrast to those obtained with intraventricular injection of noradrenaline at different ambient temperatures and during hypothalamic heating and cooling. It is therefore unlikely that noradrenaline is involved in the hyperthermic responses to PGEs. On the other hand, the results support the view that prostaglandins may be mediators of pyrogen-induced fever. 相似文献
107.
Shinkai T De Luca V Zai G Shaikh S Matsumoto C Arnold PD Hwang R King N Trakalo J Potapova N Wong G Hori H Wong AH Ohmori O Nakamura J Kennedy JL 《Psychiatric genetics》2004,14(3):177-180
OBJECTIVE: Oxidative stress such as free radical-mediated neuronal dysfunction may be involved in the pathophysiology of schizophrenia. The human glutathione peroxidase (GPX1) is a selenium-dependent enzyme, which plays an important role in the detoxification of free radicals. We therefore hypothesized that the GPX1 gene, which is located on chromosome 3p21.3, may be involved in the pathophysiology of schizophrenia. The aim of this study is to examine whether a potentially functional polymorphism, a proline (Pro) to leucine (Leu) substitution at codon 197 (Pro197Leu) of the human GPX1 gene, is associated with susceptibility to schizophrenia. METHODS: We genotyped the Pro197Leu polymorphism in a total of 113 nuclear families that had a proband with schizophrenia. Genetic association was tested using the transmission disequilibrium test (TDT), the sib transmission disequilibrium test (STDT), and the family-based association test (FBAT). RESULTS: The minor allele (Leu) frequency was calculated to be 0.282. We could not find significant transmission disequilibrium of the alleles for the Pro197Leu polymorphism in the GPX1 gene in association with the presence of schizophrenia in our family sample (TDT, chi2=0.03, degrees of freedom=1, P=0.86; combined TDT-STDT, Z'=-0.052, P=0.47; FBAT, Z=0.000, P=1.000). CONCLUSION: The results of this study suggest that the GPX1 polymorphism is unlikely to be associated with susceptibility to schizophrenia. 相似文献
108.
Izawa I Nishizawa M Tomono Y Ohtakara K Takahashi T Inagaki M 《Genes to cells : devoted to molecular & cellular mechanisms》2002,7(5):475-485
BACKGROUND: ERBIN, an ErbB2 receptor-interacting protein, belongs to a recently described family of proteins termed the LAP [leucine-rich repeats and PSD-95/dLg-A/ZO-1 (PDZ) domains] family which has essential roles in establishment of cell polarity. RESULTS: To identify new ERBIN-binding proteins, we screened a yeast two-hybrid library, using the carboxyl-terminal fragment of ERBIN containing PDZ domain as the bait, and we isolated p0071 (also called plakophilin-4) as an ERBIN-interacting protein. p0071 is a member of the p120 catenin family, which are defined as proteins with 10 armadillo repeats, and localizes along the cell-cell border. The ERBIN PDZ domain binds the COOH-terminus of p0071 containing the PDZ domain-binding sequence. Endogenous ERBIN was co-immunoprecipitated with p0071. In fully polarized Madin-Darby canine kidney (MDCK) cells, ERBIN co-localized largely with beta-catenin and partly with desmoplakin along the lateral plasma membrane domain. At these cell-cell contact regions, ERBIN co-localizes with p0071. Over-expression of the dominant active forms of Cdc42, Rac1 or RhoA, Rho family small GTPases, resulted in a marked accumulation of ERBIN at the cell-cell contacts of MDCK and HeLa cells. CONCLUSION: These results show that ERBIN interacts in vivo with p0071 and that it may be involved in the organization of adherens junctions and the desmosomes of epithelia. In addition, we demonstrated that the subcellular localization of ERBIN might be regulated by Rho family small GTPases. 相似文献
109.
Yutaka Horie Tatsuaki Hori Chisato Hirayama Kimio Hashimoto Toukichi Yumoto Kyuichi Tanikawa 《Pathology international》1987,37(8):1327-1335
A 66-year-old male with osteoclast-like giant cell tumor of the liver that arose in the non-cirrhotlc liver is presented. The liver tests were almost normal, and plasma levels of alpha-fetoprotein and carcinoembryonic antigen were within normal limits. The findings of liver scan by 99m Tc phytate, celiac angiography, and CT scans are described for the first time for this rare neoplasm, showing a large, unresectable liver tumor. Histologically, the tumor mainly consisted of osteoclast-like giant cells and mononuclear cells, which were focally arranged in a vaguely trabecular pattern and sarcomatous pattern. By an electromicroscopic study, however, no definitive evidence was obtained whether it arose from epithelial cells or nonepithellal cells. Various clinicopathological features were described and compared with previously reported cases including two cases arising in the liver. 相似文献
110.
Kazuhiro Tsukamoto Ikuyo Watanabe Tadayoshi Shiba M. Emi 《Journal of human genetics》1998,43(4):287-288
We isolated a polymorphic dinucleotide (CA) repeat sequence from a genomic clone containing the human progesterone receptor
(PGR) gene. This polymorphism will be a useful marker in the genetic study of disorders affecting female endocrine systems,
such as progesterone resistance and breast, uterine, and ovarian cancers.
Received: July 27, 1998 / Accepted: July 29, 1998 相似文献