DNA Methylation Dynamics During Differentiation, Proliferation, and Tumorigenesis in the Intestinal Tract

Overview

Journal Stem Cells Dev

Date 2015 Sep 29

PMID 26413818

Citations 9

Authors

Can-Ze Huang

Tao Yu

Qi-Kui Chen

Affiliations

Soon will be listed here.

Abstract

DNA methylation, an epigenetic control mechanism in mammals, is widely present in the intestinal tract during the differentiation and proliferation of epithelial cells. Cells in stem cell pools or villi have different patterns of DNA methylation. The process of DNA methylation is dynamic and occurs at many relevant regulatory elements during the rapid transition of stem cells into fully mature, differentiated epithelial cells. Changes in DNA methylation patterns most often take place in enhancer and promoter regions and are associated with transcription factor binding. During differentiation, enhancer regions associated with genes important to enterocyte differentiation are demethylated, activating gene expression. Abnormal patterns of DNA methylation during differentiation and proliferation in the intestinal tract can lead to the formation of aberrant crypt foci and destroy the barrier and absorptive functions of the intestinal epithelium. Accumulation of these epigenetic changes may even result in tumorigenesis. In the current review, we discuss recent findings on the association between DNA methylation and cell differentiation and proliferation in the small intestine and highlight the possible links between dysregulation of this process and tumorigenesis.

Citing Articles

Methionine deficiency and its hydroxy analogue influence chicken intestinal 3-dimensional organoid development.

Wang Y, Hou Q, Wu Y, Xu Y, Liu Y, Chen J Anim Nutr. 2022; 8(1):38-51.

PMID: 34977374 PMC: 8669257. DOI: 10.1016/j.aninu.2021.06.001.

Leptin Receptor Overlapping Transcript (LEPROT) Is Associated with the Tumor Microenvironment and a Prognostic Predictor in Pan-Cancer.

Li B, He Y, Li P, Chen X Front Genet. 2021; 12:749435.

PMID: 34804118 PMC: 8596502. DOI: 10.3389/fgene.2021.749435.

Hypermethylation of as a Novel Tumor Suppressor Involved in Tumor Growth and Prognosis in Gastric Cancer.

Sumei S, Xiangyun K, Fenrong C, Xueguang S, Sijun H, Bin B Front Cell Dev Biol. 2021; 9:624871.

PMID: 33553182 PMC: 7859350. DOI: 10.3389/fcell.2021.624871.

subspecies engineered to produce mycosporin-like amino acids in colorectal cancer prevention.

Bozkurt H, Quigley E, Kara B SAGE Open Med. 2019; 7:2050312119825784.

PMID: 30719295 PMC: 6348500. DOI: 10.1177/2050312119825784.

Genes controlling the activation of natural killer lymphocytes are epigenetically remodeled in intestinal cells from germ-free mice.

Poupeau A, Garde C, Sulek K, Citirikkaya K, Treebak J, Arumugam M FASEB J. 2018; 33(2):2719-2731.

PMID: 30303739 PMC: 6338647. DOI: 10.1096/fj.201800787R.

References

Sheaffer K, Kaestner K . Transcriptional networks in liver and intestinal development. Cold Spring Harb Perspect Biol. 2012; 4(9):a008284. PMC: 3428765. DOI: 10.1101/cshperspect.a008284. View

Eden A, Gaudet F, Waghmare A, Jaenisch R . Chromosomal instability and tumors promoted by DNA hypomethylation. Science. 2003; 300(5618):455. DOI: 10.1126/science.1083557. View

Wright N . Epithelial stem cell repertoire in the gut: clues to the origin of cell lineages, proliferative units and cancer. Int J Exp Pathol. 2000; 81(2):117-43. PMC: 2517719. DOI: 10.1046/j.1365-2613.2000.00146.x. View

Giles R, van Es J, Clevers H . Caught up in a Wnt storm: Wnt signaling in cancer. Biochim Biophys Acta. 2003; 1653(1):1-24. DOI: 10.1016/s0304-419x(03)00005-2. View

Brandeis M, Frank D, Keshet I, Siegfried Z, Mendelsohn M, Nemes A . Sp1 elements protect a CpG island from de novo methylation. Nature. 1994; 371(6496):435-8. DOI: 10.1038/371435a0. View

Carone B, Fauquier L, Habib N, Shea J, Hart C, Li R . Paternally induced transgenerational environmental reprogramming of metabolic gene expression in mammals. Cell. 2010; 143(7):1084-96. PMC: 3039484. DOI: 10.1016/j.cell.2010.12.008. View

Ueo T, Imayoshi I, Kobayashi T, Ohtsuka T, Seno H, Nakase H . The role of Hes genes in intestinal development, homeostasis and tumor formation. Development. 2012; 139(6):1071-82. DOI: 10.1242/dev.069070. View

Uthus E, Begaye A, Ross S, Zeng H . The von Hippel-Lindau (VHL) tumor-suppressor gene is down-regulated by selenium deficiency in Caco-2 cells and rat colon mucosa. Biol Trace Elem Res. 2010; 142(2):223-31. DOI: 10.1007/s12011-010-8764-4. View

Benoit Y, Pare F, Francoeur C, Jean D, Tremblay E, Boudreau F . Cooperation between HNF-1alpha, Cdx2, and GATA-4 in initiating an enterocytic differentiation program in a normal human intestinal epithelial progenitor cell line. Am J Physiol Gastrointest Liver Physiol. 2010; 298(4):G504-17. PMC: 2907224. DOI: 10.1152/ajpgi.00265.2009. View

10.

Talens R, Christensen K, Putter H, Willemsen G, Christiansen L, Kremer D . Epigenetic variation during the adult lifespan: cross-sectional and longitudinal data on monozygotic twin pairs. Aging Cell. 2012; 11(4):694-703. PMC: 3399918. DOI: 10.1111/j.1474-9726.2012.00835.x. View

11.

Segditsas S, Tomlinson I . Colorectal cancer and genetic alterations in the Wnt pathway. Oncogene. 2006; 25(57):7531-7. DOI: 10.1038/sj.onc.1210059. View

12.

Holliday R, Pugh J . DNA modification mechanisms and gene activity during development. Science. 1975; 187(4173):226-32. View

13.

Bienz M, Clevers H . Linking colorectal cancer to Wnt signaling. Cell. 2000; 103(2):311-20. DOI: 10.1016/s0092-8674(00)00122-7. View

14.

Issa J, Ahuja N, Toyota M, Bronner M, Brentnall T . Accelerated age-related CpG island methylation in ulcerative colitis. Cancer Res. 2001; 61(9):3573-7. View

15.

Barker N, van Es J, Kuipers J, Kujala P, van den Born M, Cozijnsen M . Identification of stem cells in small intestine and colon by marker gene Lgr5. Nature. 2007; 449(7165):1003-7. DOI: 10.1038/nature06196. View

16.

Farthing C, Ficz G, Ng R, Chan C, Andrews S, Dean W . Global mapping of DNA methylation in mouse promoters reveals epigenetic reprogramming of pluripotency genes. PLoS Genet. 2008; 4(6):e1000116. PMC: 2432031. DOI: 10.1371/journal.pgen.1000116. View

17.

Li V, Ng S, Boersema P, Low T, Karthaus W, Gerlach J . Wnt signaling through inhibition of β-catenin degradation in an intact Axin1 complex. Cell. 2012; 149(6):1245-56. DOI: 10.1016/j.cell.2012.05.002. View

18.

HOOPER C . Cell turnover in epithelial populations. J Histochem Cytochem. 1956; 4(6):531-40. DOI: 10.1177/4.6.531. View

19.

Vincent A, Kazmierczak C, Duchene B, Jonckheere N, Leteurtre E, Van Seuningen I . Cryosectioning the intestinal crypt-villus axis: an ex vivo method to study the dynamics of epigenetic modifications from stem cells to differentiated cells. Stem Cell Res. 2015; 14(1):105-13. DOI: 10.1016/j.scr.2014.12.002. View

20.

Toyooka S, Toyooka K, Harada K, Miyajima K, Makarla P, Sathyanarayana U . Aberrant methylation of the CDH13 (H-cadherin) promoter region in colorectal cancers and adenomas. Cancer Res. 2002; 62(12):3382-6. View