Active DNA demethylation by DNMT3A and DNMT3B in vitro and of methylated episomal DNA in transiently transfected cells

Publication date: Available online 6 October 2018

Source: Biochimica et Biophysica Acta (BBA) - Gene Regulatory Mechanisms

Author(s): Biswanath Chatterjee, Miao-Hsia Lin, Chun-Chang Chen, Kai-Lin Peng, Mu-Sheng Wu, Mei-Chun Tseng, Yu-Ju Chen, Che-Kun James Shen

Abstract

The DNA methylation program in vertebrates is an essential part of the epigenetic regulatory cascade of development, cell differentiation, and progression of diseases including cancer. While the DNA methyltransferases (DNMTs) are responsible for the in vivo conversion of cytosine (C) to methylated cytosine (5mC), demethylation of 5mC on cellular DNA could be accomplished by the combined action of the ten-eleven translocation (TET) enzymes and DNA repair. Surprisingly, the mammalian DNMTs also possess active DNA demethylation activity in vitro in a Ca²⁺- and redox conditions-dependent manner, although little is known about its molecular mechanisms and occurrence in a cellular context. In this study, we have used LC-MS/MS to track down the fate of the methyl group removed from 5mC on DNA by mouse DNMT3B in vitro and found that it becomes covalently linked to the DNA methylation catalytic cysteine of the enzyme. We also show that Ca²⁺ homeostasis-dependent but TET1/TET2/TET3/TDG-independent demethylation of methylated episomal DNA by mouse DNMT3A or DNMT3B can occur in transfected human HEK 293 and mouse embryonic stem (ES) cells. Based on these results, we present a tentative working model of Ca²⁺ and redox conditions-dependent active DNA demethylation by DNMTs. Our study substantiates the potential roles of the vertebrate DNMTs as double-edged swords in DNA methylation-demethylation during Ca²⁺-dependent physiological processes.

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The effect of countermeasures against the reaction time based concealed information test on the P300 index of knowledge recognition: A combined RT and P300-based test

Publication date: Available online 7 October 2018

Source: International Journal of Psychophysiology

Author(s): Joseph Olson, J. Peter Rosenfeld, Taewoo Kim, Ella Perrault

Abstract

Behavioral reaction time (RT) to key (probe) stimuli in a concealed information test (CIT) is usually greater than RT to irrelevant stimuli, and this difference has been utilized as a sign of recognition of concealed information. The ability to voluntarily increase irrelevant RT would appear to be an obvious countermeasure to the RT-based CIT. This study examined the effect of such countermeasure use on the simultaneously recorded P300 event related potentials. There were two blocks of trials in the present study, based on the 3-stimulus protocol. On the first trial block, half the participants were tested on concealed recognition of their phone numbers without a countermeasure. In the second block, this subset of participants were tested on their birth dates, while they applied a countermeasure consisting of the mental statement of the phrase "yes sir" prior to the button press signaling irrelevant stimulus. The other half of the subjects received the reverse order of stimulus categories. Results were that probe RT exceeded irrelevant RT in the first block, but that this relationship was reversed on the second block. In contrast, although the probe P300 exceeded the irrelevant P300 in the first block, this difference significantly increased in the second (RT countermeasure) block, leading to more detections based on P300. Thus, there was a differential effect of this novel countermeasure (directed at countering RT) on RT and P300, which actually led to improved detection with P300, suggesting that both measures might be profitably used in field applications.

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Frontal asymmetry predicts the incentive value of perceptual information

Publication date: Available online 6 October 2018

Source: International Journal of Psychophysiology

Author(s): Wiebke Käckenmester, Lara Kroencke, Jan Wacker

Abstract

Information has been suggested to convey incentive value mediated by dopaminergic systems similar to those implicated in extrinsic reward. Although the reward characteristics of information have received preliminary support by behavioral and fMRI findings, EEG correlates and individual differences have not yet been examined. In the current study, a novel perceptual paradigm was developed to probe the associations between anticipation of perceptual information and frontal electroencephalographic alpha asymmetry, i.e., a marker of approach motivation. Assuming individual differences in engaging with perceptual information, trait openness was examined as a moderator of the associations. One hundred and twenty participants viewed partly visible photos that were gradually uncovered. After they indicated state levels of confidence and curiosity, the photos were fully disclosed. During anticipation of the fully disclosed stimuli, left-lateralized asymmetry linearly increased with curiosity. Moreover, a curvilinear relationship between confidence and left-lateralized asymmetry emerged, suggesting enhanced motivational activation during medium levels of uncertainty. The curvilinear relationship was moderated by trait openness, indicating individual differences in the responsiveness to perceptual uncertainty. In summary, our findings provide novel empirical evidence for the incentive motivational value of information.

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