title: Prenatal alcohol exposure and cellular differentiation: a role for Polycomb and Trithorax group proteins in FAS phenotypes?
abstract: Exposure to alcohol significantly alters the developmental trajectory of progenitor cells and fundamentally compromises tissue formation (i.e., histogenesis). Emerging research suggests that ethanol can impair mammalian development by interfering with the execution of molecular programs governing differentiation. For example, ethanol exposure disrupts cellular migration, changes cell-cell interactions, and alters growth factor signaling pathways. Additionally, ethanol can alter epigenetic mechanisms controlling gene expression. Normally, lineage-specific regulatory factors (i.e., transcription factors) establish the transcriptional networks of each new cell type; the cell's identity then is maintained through epigenetic alterations in the way in which the DNA encoding each gene becomes packaged within the chromatin. Ethanol exposure can induce epigenetic changes that do not induce genetic mutations but nonetheless alter the course of fetal development and result in a large array of patterning defects. Two crucial enzyme complexes--the Polycomb and Trithorax proteins--are central to the epigenetic programs controlling the intricate balance between self-renewal and the execution of cellular differentiation, with diametrically opposed functions. Prenatal ethanol exposure may disrupt the functions of these two enzyme complexes, altering a crucial aspect of mammalian differentiation. Characterizing the involvement of Polycomb and Trithorax group complexes in the etiology of fetal alcohol spectrum disorders will undoubtedly enhance understanding of the role that epigenetic programming plays in this complex disorder.
authors: Department of Veterinary Physiology and Pharmacology, College of Veterinary Medicine and Biomedical Sciences, Texas A&M University, College Station, Texas, USA.
authors: Kylee J
authors: KJ
authors: Veazey
authors: Daria
authors: D
authors: Muller
authors: Michael C
authors: MC
authors: Golding
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000187:drug effects* / Q000235:genetics; D002492:Central Nervous System Depressants / Q000009:adverse effects*; D044127:Epigenesis, Genetic / Q000187:drug effects; D000431:Ethanol / Q000009:adverse effects*; D005260:Female; D063647:Fetal Alcohol Spectrum Disorders / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D046912:Multiprotein Complexes / Q000502:physiology; D051788:Myeloid-Lymphoid Leukemia Protein / Q000502:physiology*; D063146:Polycomb-Group Proteins / Q000502:physiology*; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects / Q000235:genetics / Q000378:metabolism
chemical_list: D002492:Central Nervous System Depressants; D046912:Multiprotein Complexes; D063146:Polycomb-Group Proteins; D051788:Myeloid-Lymphoid Leukemia Protein; D000431:Ethanol