Determinants of orofacial clefting II: Effects of 5-Aza-2'-deoxycytidine on gene methylation during development of the first branchial arch.

Autor: Seelan RS; Department of Molecular, Cellular and Craniofacial Biology, ULSD, University of Louisville, Louisville, KY 40202, USA. Electronic address: rsseel01@louisville.edu., Mukhopadhyay P; Department of Molecular, Cellular and Craniofacial Biology, ULSD, University of Louisville, Louisville, KY 40202, USA. Electronic address: p0mukh01@louisville.edu., Warner DR; Department of Molecular, Cellular and Craniofacial Biology, ULSD, University of Louisville, Louisville, KY 40202, USA. Electronic address: dwarn01@louisville.edu., Smolenkova IA; Department of Molecular, Cellular and Craniofacial Biology, ULSD, University of Louisville, Louisville, KY 40202, USA. Electronic address: irina.smolenkova@louisville.edu., Pisano MM; Department of Molecular, Cellular and Craniofacial Biology, ULSD, University of Louisville, Louisville, KY 40202, USA. Electronic address: drmikeky@gmail.com., Greene RM; Department of Molecular, Cellular and Craniofacial Biology, ULSD, University of Louisville, Louisville, KY 40202, USA. Electronic address: dr.bob.greene@gmail.com.
Jazyk: angličtina
Zdroj: Reproductive toxicology (Elmsford, N.Y.) [Reprod Toxicol] 2017 Jan; Vol. 67, pp. 100-110. Date of Electronic Publication: 2016 Dec 05.
DOI: 10.1016/j.reprotox.2016.11.020
Abstrakt: Defects in development of the secondary palate, which arise from the embryonic first branchial arch (1-BA), can cause cleft palate (CP). Administration of 5-Aza-2'-deoxycytidine (AzaD), a demethylating agent, to pregnant mice on gestational day 9.5 resulted in complete penetrance of CP in fetuses. Several genes critical for normal palatogenesis were found to be upregulated in 1-BA, 12h after AzaD exposure. MethylCap-Seq (MCS) analysis identified several differentially methylated regions (DMRs) in DNA extracted from AzaD-exposed 1-BAs. Hypomethylated DMRs did not correlate with the upregulation of genes in AzaD-exposed 1-BAs. However, most DMRs were associated with endogenous retroviral elements. Expression analyses suggested that interferon signaling was activated in AzaD-exposed 1-BAs. Our data, thus, suggest that a 12-h in utero AzaD exposure demethylates and activates endogenous retroviral elements in the 1-BA, thereby triggering an interferon-mediated response. This may result in the dysregulation of key signaling pathways during palatogenesis, causing CP.
(Copyright © 2016 Elsevier Inc. All rights reserved.)
Databáze: MEDLINE
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