title: Epigenetic regulation of the intestinal epithelium.
abstract: The intestinal epithelium is an ideal model system for the study of normal and pathological differentiation processes. The mammalian intestinal epithelium is a single cell layer comprising proliferative crypts and differentiated villi. The crypts contain both proliferating and quiescent stem cell populations that self-renew and produce all the differentiated cell types, which are replaced every 3-5 days. The genetics of intestinal development, homeostasis, and disease are well defined, but less is known about the contribution of epigenetics in modulating these processes. Epigenetics refers to heritable phenotypic traits, including gene expression, which are independent of mutations in the DNA sequence. We have known for several decades that human colorectal cancers contain hypomethylated DNA, but the causes and consequences of this phenomenon are not fully understood. In contrast, tumor suppressor gene promoters are often hypermethylated in colorectal cancer, resulting in decreased expression of the associated gene. In this review, we describe the role that epigenetics plays in intestinal homeostasis and disease, with an emphasis on results from mouse models. We highlight the importance of producing and analyzing next-generation sequencing data detailing the epigenome from intestinal stem cell to differentiated intestinal villus cell.
authors.affiliation: Department of Genetics and Institute for Diabetes, Obesity and Metabolism, University of Pennsylvania Perelman School of Medicine, 12-126 Translational Research Center, 3400 Civic Center Boulevard, Philadelphia, PA, 19104, USA.
authors.forename: Ellen N
authors.initials: EN
authors.lastname: Elliott
authors.affiliation: Department of Genetics and Institute for Diabetes, Obesity and Metabolism, University of Pennsylvania Perelman School of Medicine, 12-126 Translational Research Center, 3400 Civic Center Boulevard, Philadelphia, PA, 19104, USA. kaestner@mail.med.upenn.edu.
authors.forename: Klaus H
authors.initials: KH
authors.lastname: Kaestner
mesh_terms: D000818:Animals; D002454:Cell Differentiation; D002843:Chromatin / Q000378:metabolism / Q000648:ultrastructure; D015179:Colorectal Neoplasms / Q000235:genetics* / Q000473:pathology; D019175:DNA Methylation; D044127:Epigenesis, Genetic; D006657:Histones / Q000235:genetics / Q000378:metabolism; D006801:Humans; D007410:Intestinal Diseases / Q000235:genetics* / Q000473:pathology; D007413:Intestinal Mucosa / Q000166:cytology / Q000473:pathology / Q000502:physiology*; D008322:Mammals; D051379:Mice; D009374:Neoplasms, Experimental / Q000235:genetics; D009707:Nucleosomes / Q000235:genetics / Q000378:metabolism; D051880:Receptors, Notch / Q000378:metabolism; D013234:Stem Cells / Q000166:cytology / Q000502:physiology; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D060449:Wnt Signaling Pathway
chemical_list: D002843:Chromatin; D006657:Histones; D009707:Nucleosomes; D051880:Receptors, Notch; D014157:Transcription Factors
keywords: Colorectal cancer; DNA methylation; Epigenetics; Intestinal epithelium