Coordinated Activation of Candidate Proto-Oncogenes and Cancer Testes Antigens via Promoter Demethylation in Head and Neck Cancer and Lung Cancer

Background: Epigenetic alterations have been implicated in the pathogenesis of solid tumors, however, proto-oncogenes activated by promoter demethylation have been sporadically reported. We used an integrative method to analyze expression in primary head and neck squamous cell carcinoma (HNSCC) and pharmacologically demethylated cell lines to identify aberrantly demethylated and expressed candidate proto-oncogenes and cancer testes antigens in HNSCC. Methodology/Principal Findings: We noted coordinated promoter demethylation and simultaneous transcriptional upregulation of proto-oncogene candidates with promoter homology, and phylogenetic footprinting of these promoters demonstrated potential recognition sites for the transcription factor BORIS. Aberrant BORIS expression correlated with upregulation of candidate proto-oncogenes in multiple human malignancies including primary non-small cell lung cancers and HNSCC, induced coordinated proto-oncogene specific promoter demethylation and expression in non-tumorigenic cells, and transformed NIH3T3 cells. Conclusions/Significance: Coordinated, epigenetic unmasking of multiple genes with growth promoting activity occurs i

Optical and luminescence spectroscopy studies of electronic structure of Li6GdB3O9Li_6GdB_3O_9 single crystals

This article presents the study of electronic structure of Li6GdB3O9 single crystals and radiative relaxation of electronic excitations in them. The investigation was performed by the means of low-temperature optical and luminescence far-ultraviolet spectroscopy upon excitation by synchrotron radiation. On the basis of the low-temperature (T = 10 and 30 K) spectra of the reflection, recorded in the present research and the dispersions of the complex optical functions of View the MathML sourceεˆ(E),nˆ(E) and μ(E)μ(E), calculated in the framework of the oscillator model, we have determined the parameters of the electronic structure of the Li6GdB3O9 crystals as follows. The value of the minimum energy for the interband transitions in the boron–oxygen framework is View the MathML sourceEg=9.42eV, the energy position of the first excitonic peak in the excitation spectra for anionic excitons is View the MathML sourceEn=1=7.46eV, the minimum threshold energy for excitation of excitons in linear chains of the Gd3+ cations is View the MathML sourceEc=6.80eV. The excitation spectra of an intrinsic luminescence of Li6GdB3O9 crystals, recorded at 10 K in the range of the optical charge-transfer transitions O–Gd have a band with the maximum at View the MathML sourceECT=6.57eV

Functional Phosphorylation Sites in the C-Terminal Region of the Multivalent Multifunctional Transcriptional Factor CTCF

CTCF is a widely expressed and highly conserved multi-Zn-finger (ZF) nuclear factor. Binding to various CTCF target sites (CTSs) is mediated by combinatorial contributions of different ZFs. Different CTSs mediate distinct CTCF functions in transcriptional regulation, including promoter repression or activation and hormone-responsive gene silencing. In addition, the necessary and sufficient core sequences of diverse enhancer-blocking (insulator) elements, including CpG methylation-sensitive ones, have recently been pinpointed to CTSs. To determine whether a posttranslational modification may modulate CTCF functions, we studied CTCF phosphorylation. We demonstrated that most of the modifications that occur at the carboxy terminus in vivo can be reproduced in vitro with casein kinase II (CKII). Major modification sites map to four serines within the S(604)KKEDS(609)S(610)DS(612)E motif that is highly conserved in vertebrates. Specific mutations of these serines abrogate phosphorylation of CTCF in vivo and CKII-induced phosphorylation in vitro. In addition, we showed that completely preventing phosphorylation by substituting all serines within this site resulted in markedly enhanced repression of the CTS-bearing vertebrate c-myc promoters, but did not alter CTCF nuclear localization or in vitro DNA-binding characteristics assayed with c-myc CTSs. Moreover, these substitutions manifested a profound effect on negative cell growth regulation by wild-type CTCF. CKII may thus be responsible for attenuation of CTCF activity, either acting on its own or by providing the signal for phosphorylation by other kinases and for CTCF-interacting protein partners