Enhancer, Transcriptional, and Cell Fate Plasticity Precedes Intestinal Determination During Endoderm Development

Overview

Journal Genes Dev

Specialty Molecular Biology

Date 2018 Oct 28

PMID 30366903

Citations 24

Authors

Kushal K Banerjee

Madhurima Saxena

Namit Kumar

Lei Chen

Alessia Cavazza

Natalie H Toke

Nicholas K ONeill

Shariq Madha

Unmesh Jadhav

Michael P Verzi

Ramesh A Shivdasani

Affiliations

Soon will be listed here.

Abstract

After acquiring competence for selected cell fates, embryonic primordia may remain plastic for variable periods before tissue identity is irrevocably determined (commitment). We investigated the chromatin basis for these developmental milestones in mouse endoderm, a tissue with recognizable rostro-caudal patterning and transcription factor (TF)-dependent interim plasticity. Foregut-specific enhancers are as accessible and active in early midgut as in foregut endoderm, and intestinal enhancers and identity are established only after ectopic -regulatory elements are decommissioned. Depletion of the intestinal TF CDX2 before this element transition stabilizes foregut enhancers, reinforces ectopic transcriptional programs, and hence imposes foregut identities on the midgut. Later in development, as the window of chromatin plasticity elapses, CDX2 depletion weakens intestinal, without strengthening foregut, enhancers. Thus, midgut endoderm is primed for heterologous cell fates, and TFs act on a background of shifting chromatin access to determine intestinal at the expense of foregut identity. Similar principles likely govern other fate commitments.

Citing Articles

A MTA2-SATB2 chromatin complex restrains colonic plasticity toward small intestine by retaining HNF4A at colonic chromatin.

Gu W, Huang X, Singh P, Li S, Lan Y, Deng M Nat Commun. 2024; 15(1):3595.

PMID: 38678016 PMC: 11055869. DOI: 10.1038/s41467-024-47738-y.

Tissue-location-specific transcription programs drive tumor dependencies in colon cancer.

Yang L, Tu L, Bisht S, Mao Y, Petkovich D, Thursby S Nat Commun. 2024; 15(1):1384.

PMID: 38360902 PMC: 10869357. DOI: 10.1038/s41467-024-45605-4.

DNA methylation restricts coordinated germline and neural fates in embryonic stem cell differentiation.

Schulz M, Teissandier A, De La Mata Santaella E, Armand M, Iranzo J, El Marjou F Nat Struct Mol Biol. 2024; 31(1):102-114.

PMID: 38177678 DOI: 10.1038/s41594-023-01162-w.

Invasive stratified mucin-producing carcinoma of the colorectum: expanding the morphologic spectrum of large bowel cancer.

Auld F, Moyana T Diagn Pathol. 2023; 18(1):113.

PMID: 37853375 PMC: 10585790. DOI: 10.1186/s13000-023-01396-8.

Multiple roles and regulatory mechanisms of the transcription factor HNF4 in the intestine.

Vemuri K, Radi S, Sladek F, Verzi M Front Endocrinol (Lausanne). 2023; 14:1232569.

PMID: 37635981 PMC: 10450339. DOI: 10.3389/fendo.2023.1232569.

References

Anders S, Pyl P, Huber W . HTSeq--a Python framework to work with high-throughput sequencing data. Bioinformatics. 2014; 31(2):166-9. PMC: 4287950. DOI: 10.1093/bioinformatics/btu638. View

Raghoebir L, Bakker E, Mills J, Swagemakers S, Buscop-van Kempen M, Boerema-de Munck A . SOX2 redirects the developmental fate of the intestinal epithelium toward a premature gastric phenotype. J Mol Cell Biol. 2012; 4(6):377-85. PMC: 3523556. DOI: 10.1093/jmcb/mjs030. View

Subramanian A, Tamayo P, Mootha V, Mukherjee S, Ebert B, Gillette M . Gene set enrichment analysis: a knowledge-based approach for interpreting genome-wide expression profiles. Proc Natl Acad Sci U S A. 2005; 102(43):15545-50. PMC: 1239896. DOI: 10.1073/pnas.0506580102. View

Yasugi S, Mizuno T . Molecular analysis of endoderm regionalization. Dev Growth Differ. 2008; 50 Suppl 1:S79-96. DOI: 10.1111/j.1440-169X.2008.00984.x. View

Grainger S, Savory J, Lohnes D . Cdx2 regulates patterning of the intestinal epithelium. Dev Biol. 2010; 339(1):155-65. DOI: 10.1016/j.ydbio.2009.12.025. View

Gao N, White P, Kaestner K . Establishment of intestinal identity and epithelial-mesenchymal signaling by Cdx2. Dev Cell. 2009; 16(4):588-99. PMC: 2673200. DOI: 10.1016/j.devcel.2009.02.010. View

Langmead B, Salzberg S . Fast gapped-read alignment with Bowtie 2. Nat Methods. 2012; 9(4):357-9. PMC: 3322381. DOI: 10.1038/nmeth.1923. View

Grapin-Botton A, Melton D . Endoderm development: from patterning to organogenesis. Trends Genet. 2000; 16(3):124-30. DOI: 10.1016/s0168-9525(99)01957-5. View

Wells J, Melton D . Vertebrate endoderm development. Annu Rev Cell Dev Biol. 1999; 15:393-410. DOI: 10.1146/annurev.cellbio.15.1.393. View

10.

Verzi M, Shin H, He H, Sulahian R, Meyer C, Montgomery R . Differentiation-specific histone modifications reveal dynamic chromatin interactions and partners for the intestinal transcription factor CDX2. Dev Cell. 2010; 19(5):713-26. PMC: 3001591. DOI: 10.1016/j.devcel.2010.10.006. View

11.

Harfe B, Scherz P, Nissim S, Tian H, McMahon A, Tabin C . Evidence for an expansion-based temporal Shh gradient in specifying vertebrate digit identities. Cell. 2004; 118(4):517-28. DOI: 10.1016/j.cell.2004.07.024. View

12.

Silberg D, Sullivan J, Kang E, Swain G, Moffett J, Sund N . Cdx2 ectopic expression induces gastric intestinal metaplasia in transgenic mice. Gastroenterology. 2002; 122(3):689-96. DOI: 10.1053/gast.2002.31902. View

13.

Kazakevych J, Sayols S, Messner B, Krienke C, Soshnikova N . Dynamic changes in chromatin states during specification and differentiation of adult intestinal stem cells. Nucleic Acids Res. 2017; 45(10):5770-5784. PMC: 5449638. DOI: 10.1093/nar/gkx167. View

14.

Silberg D, Swain G, Suh E, Traber P . Cdx1 and cdx2 expression during intestinal development. Gastroenterology. 2000; 119(4):961-71. DOI: 10.1053/gast.2000.18142. View

15.

Grapin-Botton A . Antero-posterior patterning of the vertebrate digestive tract: 40 years after Nicole Le Douarin's PhD thesis. Int J Dev Biol. 2005; 49(2-3):335-47. DOI: 10.1387/ijdb.041946ag. View

16.

Dobin A, Davis C, Schlesinger F, Drenkow J, Zaleski C, Jha S . STAR: ultrafast universal RNA-seq aligner. Bioinformatics. 2012; 29(1):15-21. PMC: 3530905. DOI: 10.1093/bioinformatics/bts635. View

17.

Sulahian R, Chen J, Arany Z, Jadhav U, Peng S, Rustgi A . SOX15 governs transcription in human stratified epithelia and a subset of esophageal adenocarcinomas. Cell Mol Gastroenterol Hepatol. 2015; 1(6):598-609.e6. PMC: 4620585. DOI: 10.1016/j.jcmgh.2015.07.009. View

18.

Mutoh H, Hakamata Y, Sato K, Eda A, Yanaka I, Honda S . Conversion of gastric mucosa to intestinal metaplasia in Cdx2-expressing transgenic mice. Biochem Biophys Res Commun. 2002; 294(2):470-9. DOI: 10.1016/S0006-291X(02)00480-1. View

19.

Liu T, Ortiz J, Taing L, Meyer C, Lee B, Zhang Y . Cistrome: an integrative platform for transcriptional regulation studies. Genome Biol. 2011; 12(8):R83. PMC: 3245621. DOI: 10.1186/gb-2011-12-8-r83. View

20.

Li H, Handsaker B, Wysoker A, Fennell T, Ruan J, Homer N . The Sequence Alignment/Map format and SAMtools. Bioinformatics. 2009; 25(16):2078-9. PMC: 2723002. DOI: 10.1093/bioinformatics/btp352. View