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Prenatal alcohol exposure has profound effects on neuronal growth and development. Poly-ADP Ribose Polymerase (PARP) enzymes are perhaps unique in the field of epigenetics in that they directly participate in histone modifications, transcription factor modifications, DNA methylation/demethylation and are highly inducible by ethanol. It was our hypothesis that ethanol would induce PARP enzymatic activity leading to alterations in neurodevelopmental gene expression. Mouse E18 cortical neurons were treated with ethanol, PARP inhibitors, and nuclear hormone receptor transcription factor PPARγ agonists and antagonists. Subsequently, we measured PARP activity and changes in Bdnf, OKSM (Oct4, Klf4, Sox2, c-Myc), DNA methylating/demethylating factors, and Pparγ mRNA expression, promoter 5-methylcytosine (5MC) and 5-hydroxymethylcytosine (5HMC), and PPARγ promoter binding. We found that ethanol reduced Bdnf4, 9a, and Klf4 mRNA expression, and increased c-Myc expression. These changes were reversed with a PARP inhibitor. In agreement with its role in DNA demethylation PARP inhibition increased 5MC levels at the c-Myc promoter. In addition, we found that inhibition of PARP enzymatic activity increased PPARγ promoter binding, and this corresponded to increased Bdnf and Klf4 mRNA expression. Our results suggest that PARP participates in DNA demethylation and reduces PPARγ promoter binding. The current study underscores the importance of PARP in ethanol-induced changes to neurodevelopmental gene expression., Competing Interests: The authors have no conflicts of interest to disclose., (Published by Elsevier Ltd.)

Erythroid differentiation is a tightly regulated multi-step process that has not been fully elucidated. We previously reported that a siRNA screened from random siRNA library, siRNA clone-67, induced erythroid differentiation in human erythroleukemia K-562cell line. Here we identified that human CCDC12 (coiled-coil domain containing 12) is a target of siRNA clone-67, by target capture with biotinylated siRNA. Over-expression of CCDC12 in K-562cell up-regulated the expression of CD235, ε-globin and γ-globin, accelerated cell growth, and slightly down-regulated the expression of GATA-2. Knockdown of CCDC12 slowed down the cell growth. These data indicate that CCDC12 is a new participant that promotes early erythroid differentiation., (Copyright © 2011 Elsevier Ltd. All rights reserved.)