Hepatocyte nuclear factor-1beta (HNF-1beta) is a transcription factor that regulates gene expression in the kidney, liver, pancreas, and other epithelial organs. Mutations of HNF-1beta lead to a syndrome of inherited renal cysts and diabetes and are also a common cause of sporadic renal dysplasia. The full complement of target genes responsible for the functions of HNF-1beta, however, is incompletely defined. Using a functional genomics approach involving chromatin immunoprecipitation and promoter arrays, combined with gene expression profiling, we found that an HNF-1beta target gene in the kidney is kinesin family member 12 (Kif12), a gene previously identified as a candidate modifier gene in the cpk mouse model of polycystic kidney disease. Mutations of HNF-1beta inhibited Kif12 transcription in both cultured cells and knockout mice by altering co-factor recruitment and histone modification. Because kinesin-12 family members participate in orienting cell division, downregulation of Kif12 may underlie the abnormal planar cell polarity observed in cystic kidney diseases.
"Cys1 is responsible for congenital polycystic kidney (CPK) disease (Tao et al., 2009) and is involved in ciliogenesis and polarization of cholangiocytes (Raynaud et al., 2011), whereas Glis3 is implicated in polycystic disease in both kidney (Kang et al., 2009a) and pancreas (Kang et al., 2009b). Among these genes, Kif12, Pkhd1, Pkd2 and Bicc1 were identified as direct Hnf1b targets in the kidney (Gong et al., 2009; Gresh et al., 2004; Verdeguer et al., 2010). Thus, we analyzed whether Hnf1b could be a major regulator of these genes in the pancreas by ChIP experiments on E12.5 pancreata (Fig. 5V). "
"Additionally, it has been reported that the pathologic conditions in a polycystic kidney disease mouse model may be caused by the inhibition of KIF12 transcription resulting from a mutation in HNF-1beta, a regulator of Kif12 expression (Gong et al., 2009). Moreover, numerous studies have suggested a relationship between disorders in kinesin expression and tumorigenesis (Yu and Feng, 2010). "
[Show abstract][Hide abstract] ABSTRACT: Intracellular transport is spatiotemporally controlled by microtubule-dependent motor proteins, including kinesins. In order to elucidate the mechanisms controlling kinesin expression, it is important to analyze their genomic regulatory regions. In this study, we cloned the neuronal tissue-specific kinesin in medaka fish and generated transgenic fish which mimic endogenous neuronal kinesin expression in order to elucidate the mechanisms which regulate kinesin expression. Searches for medaka neuronal orthologues by RT-PCR identified a candidate gene expressed only in neuronal tissues. Using BAC clones, we determined the cDNA sequence and the gene structure of the candidate neuronal kinesin. Evolutionary analysis indicated that the candidate gene encoded medaka KIF5Aa. The endogenous medaka orthologue was found to be expressed only in the nervous system, including the brain and spinal cord, while expression of KIF5Ab was not exclusive to neuronal tissues. Transgenic (Tg) medaka that expressed EGFP under the control of the 6.9kbp 5' and 1.9kbp 3' flanking regions of the KIF5Aa gene showed characteristic expression throughout the nervous system, including the brain, spinal cord, olfactory pit, eye and cranial nerve. Immunohistological analysis showed that EGFP expression in Tg fish co-localized with expression of HuC/D, a neuronal marker. These results demonstrate that the 6.9kbp 5' and 1.9kbp 3' flanking regions of medaka KIF5Aa have neuronal-specific promoter activity mimicking endogenous expression of medaka KIF5Ab. This transgenic fish strain will be useful for further functional analysis of the effects of these regulatory regions on gene expression.
Brain research 09/2012; 1480:12-21. DOI:10.1016/j.brainres.2012.08.047 · 2.84 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: New data on the energies and quantum defects of the highly excited Rydberg levels of thallium are presented using the two-step resonant excitation spectroscopic technique. The spectra were observed using two dye lasers simultaneously pumped by the SHG 532 nm and THG 355 nm of a Nd:YAG laser in conjunction with a thermionic diode ion detector. The Rydberg series 6s2np 2P1/2 (15⩽n⩽31) and np 2P3/2 (15⩽n⩽56) have been studied via the 6s2 7s 2S1/2 intermediate state. The first ionization potential is derived as 49266.66(5) cm−1, which is in good agreement with the earlier work. The relative intensities of the np 2P1/2,3/2 series decrease monotonically and follow the 1/n2.3 scaling.
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