title: Transcriptional heterogeneity in the lactase gene within cell-type is linked to the epigenome.
abstract: Transcriptional variation in histologically- and genetically- identical cells is a widespread phenomenon in tissues, yet the processes conferring this heterogeneity are not well understood. To identify contributing factors, we analyzed epigenetic profiles associated with the in vivo transcriptional gradient of the mouse lactase gene (Lct), which occurs in enterocytes along the proximal-to-distal axis of the small intestine. We found that epigenetic signatures at enhancer and promoter elements aligns with transcriptional variation of Lct in enterocytes. Age and phenotype-specific environmental cues (lactose exposure after weaning) induced changes to epigenetic modifications and CTCF binding at select regulatory elements, which corresponded to the alterations in the intestinal Lct mRNA gradient. Thus, epigenetic modifications in combination with CTCF binding at regulatory elements account for the transcriptional gradient in Lct in cells of the same type. Epigenetic divergence within enterocytes may contribute to the functional specialization of intestinal subregions.
authors.affiliation: Krembil Family Epigenetics Laboratory, Centre for Addiction and Mental Health, Toronto, Ontario, Canada.
authors.forename: Edward
authors.initials: E
authors.lastname: Oh
authors.affiliation: Krembil Family Epigenetics Laboratory, Centre for Addiction and Mental Health, Toronto, Ontario, Canada.
authors.forename: Richie
authors.initials: R
authors.lastname: Jeremian
authors.affiliation: Krembil Family Epigenetics Laboratory, Centre for Addiction and Mental Health, Toronto, Ontario, Canada.
authors.forename: Gabriel
authors.initials: G
authors.lastname: Oh
authors.affiliation: Krembil Family Epigenetics Laboratory, Centre for Addiction and Mental Health, Toronto, Ontario, Canada.
authors.forename: Daniel
authors.initials: D
authors.lastname: Groot
authors.affiliation: Krembil Family Epigenetics Laboratory, Centre for Addiction and Mental Health, Toronto, Ontario, Canada.
authors.forename: Miki
authors.initials: M
authors.lastname: Susic
authors.affiliation: Center for Epigenetics, Van Andel Research Institute, Grand Rapids, MI, USA.
authors.forename: KwangHo
authors.initials: K
authors.lastname: Lee
authors.affiliation: Center for Epigenetics, Van Andel Research Institute, Grand Rapids, MI, USA.
authors.forename: Kelly
authors.initials: K
authors.lastname: Foy
authors.affiliation: Center for Epigenetics, Van Andel Research Institute, Grand Rapids, MI, USA.
authors.forename: Peter W
authors.initials: PW
authors.lastname: Laird
authors.affiliation: Krembil Family Epigenetics Laboratory, Centre for Addiction and Mental Health, Toronto, Ontario, Canada.
authors.forename: Arturas
authors.initials: A
authors.lastname: Petronis
authors.affiliation: Krembil Family Epigenetics Laboratory, Centre for Addiction and Mental Health, Toronto, Ontario, Canada.|Center for Neurodegenerative Science, Van Andel Research Institute, Grand Rapids, MI, USA.
authors.forename: Viviane
authors.initials: V
authors.lastname: Labrie
mesh_terms: D000818:Animals; D000076246:CCCTC-Binding Factor / Q000378:metabolism; D004742:Enhancer Elements, Genetic; D020895:Enterocytes / Q000187:drug effects / Q000378:metabolism*; D044127:Epigenesis, Genetic; D018507:Gene Expression Regulation, Developmental; D043322:Lactase / Q000235:genetics* / Q000378:metabolism; D007785:Lactose / Q000494:pharmacology; D051379:Mice; D008810:Mice, Inbred C57BL; D011401:Promoter Regions, Genetic; D012333:RNA, Messenger / Q000235:genetics* / Q000378:metabolism
chemical_list: D000076246:CCCTC-Binding Factor; D012333:RNA, Messenger; D043322:Lactase; D007785:Lactose