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Enterocyte-specific regulation of the apical nutrient transporter SLC6A19 (B0AT1) by transcriptional and epigenetic networks

Tümer, Emrah; Bröer, Angelika; Balkrishna, Sarojini; Jülich, Torsten; Bröer, Stefan

Description

Enterocytes are specialized to absorb nutrients from the lumen of the small intestine by expressing a select set of genes to maximize the uptake of nutrients. They develop from stem cells in the crypt and differentiate into mature enterocytes while moving along the crypt-villus axis. Using, as an example, the Slc6a19 gene, encoding the neutral amino acid transporter B0AT1, we studied regulation of the gene by transcription factors and epigenetic factors in the intestine. To investigate this...[Show more]

dc.contributor.authorTümer, Emrah
dc.contributor.authorBröer, Angelika
dc.contributor.authorBalkrishna, Sarojini
dc.contributor.authorJülich, Torsten
dc.contributor.authorBröer, Stefan
dc.date.accessioned2014-08-22T05:44:45Z
dc.date.available2014-10-11T13:10:20Z
dc.identifier.issn0021-9258
dc.identifier.urihttp://hdl.handle.net/1885/11964
dc.description.abstractEnterocytes are specialized to absorb nutrients from the lumen of the small intestine by expressing a select set of genes to maximize the uptake of nutrients. They develop from stem cells in the crypt and differentiate into mature enterocytes while moving along the crypt-villus axis. Using, as an example, the Slc6a19 gene, encoding the neutral amino acid transporter B0AT1, we studied regulation of the gene by transcription factors and epigenetic factors in the intestine. To investigate this question we used a fractionation method to separate mature enterocytes from crypt cells and analysed gene expression. Transcription factors HNF1a and HNF4a activate transcription of the Slc6a19 gene in villus enterocytes, while high levels of SOX9 repress expression in the crypts. CpG dinucleotides in the proximal promoter were highly methylated in the crypt and fully de-methylated in the villus. Furthermore, histone modification H3K27Ac, indicating an active promo! ter, was prevalent in villus cells but barely detectable in crypt cells. The results suggest that Slc6a19 expression in the intestine is regulated at three different levels involving promoter methylation, histone modification and opposing transcription factors.
dc.format23 pages
dc.publisherAmerican Society for Biochemistry and Molecular Biology
dc.rightshttp://www.sherpa.ac.uk/romeo/issn/0021-9258/ "... author cannot archive pre-print (ie pre-refereeing), author can archive post-print (ie final draft post-refereeing) after 12 months embargo, author cannot archive publisher's version/PDF..." from SHERPA/RoMEO site (as at 8/07/14)
dc.sourceJournal of Biological Chemistry 288.47 (2013): 33813-23
dc.subjectamino acids transport
dc.subjectchromatin histone modification
dc.subjectDNA methylation
dc.subjectgene expression
dc.subjectintestinal epithelium
dc.subjecttranscription factor
dc.titleEnterocyte-specific regulation of the apical nutrient transporter SLC6A19 (B0AT1) by transcriptional and epigenetic networks
dc.typeJournal article
local.identifier.citationvolume288
dc.date.issued2013-10-11
local.identifier.absfor060400 - GENETICS
local.identifier.absfor060101 - Analytical Biochemistry
local.identifier.absfor110300 - CLINICAL SCIENCES
local.identifier.ariespublicationf5625xPUB4714
local.publisher.urlhttp://www.asbmb.org/
local.type.statusAccepted Version
local.contributor.affiliationBröer, S., ANU Research School of Biology
dc.relationhttp://purl.org/au-research/grants/nhmrc/585479
local.identifier.essn1083-351X
local.bibliographicCitation.issue47
local.bibliographicCitation.startpage33813
local.bibliographicCitation.lastpage33823
local.identifier.doi10.1074/jbc.M113.482760
dc.date.updated2015-12-11T09:08:41Z
local.identifier.scopusID2-s2.0-84888338310
local.identifier.thomsonID000327250200026
CollectionsANU Research Publications

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