Browsing by Subject "Histone modification"

Now showing 1 - 3 of 3
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    Environmental Alterations of Epigenetics Prior to the Birth
    (Elsevier, 2014) Lo, Chiao-Ling; Zhou, Feng C.; Anatomy, Cell Biology and Physiology, School of Medicine
    The etiology of many brain diseases remains allusive to date after intensive investigation of genomic background and symptomatology from the day of birth. Emerging evidences indicate that a third factor, epigenetics prior to the birth, can exert profound influence on the development and functioning of the brain and over many neurodevelopmental syndromes. This chapter reviews how aversive environmental exposure to parents might predispose or increase vulnerability of offspring to neurodevelopmental deficit through alteration of epigenetics. These epigenetic altering environmental factors will be discussed in the category of addictive agents, nutrition or diet, prescriptive medicine, environmental pollutant, and stress. Epigenetic alterations induced by these aversive environmental factors cover all aspects of epigenetics including DNA methylation, histone modification, noncoding RNA, and chromatin modification. Next, the mechanisms how these environmental inputs influence epigenetics will be discussed. Finally, how environmentally altered epigenetic marks affect neurodevelopment is exemplified by the alcohol-induced fetal alcohol syndrome. It is hoped that a thorough understanding of the nature of prenatal epigenetic inputs will enable researchers with a clear vision to better unravel neurodevelopmental deficit, late-onset neuropsychiatric diseases, or idiosyncratic mental disorders.
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    Epigenetic regulation of the neural transcriptome and alcohol interference during development
    (Frontiers Media, 2014-08-26) Resendiz, Marisol; Mason, Stephen; Lo, Chiao-Ling; Zhou, Feng C.; Anatomy, Cell Biology and Physiology, School of Medicine
    Alcohol intoxicated cells broadly alter their metabolites - among them methyl and acetic acid can alter the DNA and histone epigenetic codes. Together with the promiscuous effect of alcohol on enzyme activities (including DNA methyltransferases) and the downstream effect on microRNA and transposable elements, alcohol is well placed to affect intrinsic transcriptional programs of developing cells. Considering that the developmental consequences of early alcohol exposure so profoundly affect neural systems, it is not unfounded to reason that alcohol exploits transcriptional regulators to challenge canonical gene expression and in effect, intrinsic developmental pathways to achieve widespread damage in the developing nervous system. To fully evaluate the role of epigenetic regulation in alcohol-related developmental disease, it is important to first gather the targets of epigenetic players in neurodevelopmental models. Here, we attempt to review the cellular and genomic windows of opportunity for alcohol to act on intrinsic neurodevelopmental programs. We also discuss some established targets of fetal alcohol exposure and propose pathways for future study. Overall, this review hopes to illustrate the known epigenetic program and its alterations in normal neural stem cell development and further, aims to depict how alcohol, through neuroepigenetics, may lead to neurodevelopmental deficits observed in fetal alcohol spectrum disorders.
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    Quantitative Analysis of Dynamic Protein Interactions during Transcription Reveals a Role for Casein Kinase II in Polymerase-associated Factor (PAF) Complex Phosphorylation and Regulation of Histone H2B Monoubiquitylation
    (American Society for Biochemistry and Molecular Biology, 2016-06-24) Bedard, Lynn Glowczewski; Dronamraju, Raghuvar; Kerschner, Jenny L.; Hunter, Gerald O.; Axley, Elizabeth DeVlieger; Boyd, Asha K.; Strahl, Brian D.; Mosley, Amber L.; Biochemistry and Molecular Biology, School of Medicine
    Using affinity purification MS approaches, we have identified a novel role for casein kinase II (CKII) in the modification of the polymerase associated factor complex (PAF-C). Our data indicate that the facilitates chromatin transcription complex (FACT) interacts with CKII and may facilitate PAF complex phosphorylation. Posttranslational modification analysis of affinity-isolated PAF-C shows extensive CKII phosphorylation of all five subunits of PAF-C, although CKII subunits were not detected as interacting partners. Consistent with this, recombinant CKII or FACT-associated CKII isolated from cells can phosphorylate PAF-C in vitro, whereas no intrinsic kinase activity was detected in PAF-C samples. Significantly, PAF-C purifications combined with stable isotope labeling in cells (SILAC) quantitation for PAF-C phosphorylation from wild-type and CKII temperature-sensitive strains (cka1Δ cka2–8) showed that PAF-C phosphorylation at consensus CKII sites is significantly reduced in cka1Δ cka2–8 strains. Consistent with a role of CKII in FACT and PAF-C function, we show that decreased CKII function in vivo results in decreased levels of histone H2B lysine 123 monoubiquitylation, a modification dependent on FACT and PAF-C. Taken together, our results define a coordinated role of CKII and FACT in the regulation of RNA polymerase II transcription through chromatin via phosphorylation of PAF-C.