schliessen

Filtern

 

Bibliotheken

Maternal diet and aging alter the epigenetic control of a promoter-enhancer interaction at the Hnf4a gene in rat pancreatic islets.

Environmental factors interact with the genome throughout life to determine gene expression and, consequently, tissue function and disease risk. One such factor that is known to play an important role in determining long-term metabolic health is diet during critical periods of development. Epigeneti... Full description

Journal Title: Proceedings of the National Academy of Sciences of the United States of America March 29, 2011, Vol.108(13), pp.5449-5454
Main Author: Sandovici, Ionel
Other Authors: Smith, Noel H , Nitert, Marloes Dekker , Ackers-Johnson, Matthew , Uribe-Lewis, Santiago , Ito, Yoko , Jones, R Huw , Marquez, Victor E , Cairns, William , Tadayyon, Mohammed , O'Neill, Laura P , Murrell, Adele , Ling, Charlotte , Constância, Miguel , Ozanne, Susan E
Format: Electronic Article Electronic Article
Language: English
Subjects:
ID: E-ISSN: 1091-6490 ; DOI: 1091-6490 ; DOI: 10.1073/pnas.1019007108
Link: http://search.proquest.com/docview/859497508/?pq-origsite=primo
Zum Text:
SendSend as email Add to Book BagAdd to Book Bag
Staff View
recordid: proquest859497508
title: Maternal diet and aging alter the epigenetic control of a promoter-enhancer interaction at the Hnf4a gene in rat pancreatic islets.
format: Article
creator:
  • Sandovici, Ionel
  • Smith, Noel H
  • Nitert, Marloes Dekker
  • Ackers-Johnson, Matthew
  • Uribe-Lewis, Santiago
  • Ito, Yoko
  • Jones, R Huw
  • Marquez, Victor E
  • Cairns, William
  • Tadayyon, Mohammed
  • O'Neill, Laura P
  • Murrell, Adele
  • Ling, Charlotte
  • Constância, Miguel
  • Ozanne, Susan E
subjects:
  • Aging–Physiology
  • Animals–Genetics
  • Cell Line–Cytology
  • DNA Methylation–Physiology
  • Diet–Physiology
  • Enhancer Elements, Genetic–Physiology
  • Epigenesis, Genetic–Physiology
  • Female–Physiology
  • Hepatocyte Nuclear Factor 4–Physiology
  • Islets of Langerhans–Physiology
  • Maternal Exposure–Physiology
  • Promoter Regions, Genetic–Physiology
  • Rats–Physiology
  • Transcriptional Activation–Physiology
  • Hepatocyte Nuclear Factor 4
  • Hnf4a Protein, Rat
ispartof: Proceedings of the National Academy of Sciences of the United States of America, March 29, 2011, Vol.108(13), pp.5449-5454
description: Environmental factors interact with the genome throughout life to determine gene expression and, consequently, tissue function and disease risk. One such factor that is known to play an important role in determining long-term metabolic health is diet during critical periods of development. Epigenetic regulation of gene expression has been implicated in mediating these programming effects of early diet. The precise epigenetic mechanisms that underlie these effects remain largely unknown. Here, we show that the transcription factor Hnf4a, which has been implicated in the etiology of type 2 diabetes (T2D), is epigenetically regulated by maternal diet and aging in rat islets. Transcriptional activity of Hnf4a in islets is restricted to the distal P2 promoter through its open chromatin configuration and an islet-specific interaction between the P2 promoter and a downstream enhancer. Exposure to suboptimal nutrition during early development leads to epigenetic silencing at the enhancer region, which weakens the P2 promoter-enhancer interaction and results in a permanent reduction in Hnf4a expression. Aging leads to progressive epigenetic silencing of the entire Hnf4a locus in islets, an effect that is more pronounced in rats exposed to a poor maternal diet. Our findings provide evidence for environmentally induced epigenetic changes at the Hnf4a enhancer that alter its interaction with the P2 promoter, and consequently determine T2D risk. We therefore propose that environmentally induced changes in promoter-enhancer interactions represent a fundamental epigenetic mechanism by which nutrition and aging can influence long-term health. [PUBLICATION ]
language: eng
source:
identifier: E-ISSN: 1091-6490 ; DOI: 1091-6490 ; DOI: 10.1073/pnas.1019007108
fulltext: fulltext
issn:
  • 10916490
  • 1091-6490
url: Link


@attributes
ID701403308
RANK0.07
NO1
SEARCH_ENGINEprimo_central_multiple_fe
SEARCH_ENGINE_TYPEPrimo Central Search Engine
LOCALfalse
PrimoNMBib
record
control
sourcerecordid859497508
sourceidproquest
recordidTN_proquest859497508
sourcesystemOther
pqid859497508
display
typearticle
titleMaternal diet and aging alter the epigenetic control of a promoter-enhancer interaction at the Hnf4a gene in rat pancreatic islets.
creatorSandovici, Ionel ; Smith, Noel H ; Nitert, Marloes Dekker ; Ackers-Johnson, Matthew ; Uribe-Lewis, Santiago ; Ito, Yoko ; Jones, R Huw ; Marquez, Victor E ; Cairns, William ; Tadayyon, Mohammed ; O'Neill, Laura P ; Murrell, Adele ; Ling, Charlotte ; Constância, Miguel ; Ozanne, Susan E
contributorSandovici, Ionel (correspondence author) ; Sandovici, Ionel (record owner)
ispartofProceedings of the National Academy of Sciences of the United States of America, March 29, 2011, Vol.108(13), pp.5449-5454
identifier
subjectAging–Physiology ; Animals–Genetics ; Cell Line–Cytology ; DNA Methylation–Physiology ; Diet–Physiology ; Enhancer Elements, Genetic–Physiology ; Epigenesis, Genetic–Physiology ; Female–Physiology ; Hepatocyte Nuclear Factor 4–Physiology ; Islets of Langerhans–Physiology ; Maternal Exposure–Physiology ; Promoter Regions, Genetic–Physiology ; Rats–Physiology ; Transcriptional Activation–Physiology ; Hepatocyte Nuclear Factor 4 ; Hnf4a Protein, Rat
languageeng
source
descriptionEnvironmental factors interact with the genome throughout life to determine gene expression and, consequently, tissue function and disease risk. One such factor that is known to play an important role in determining long-term metabolic health is diet during critical periods of development. Epigenetic regulation of gene expression has been implicated in mediating these programming effects of early diet. The precise epigenetic mechanisms that underlie these effects remain largely unknown. Here, we show that the transcription factor Hnf4a, which has been implicated in the etiology of type 2 diabetes (T2D), is epigenetically regulated by maternal diet and aging in rat islets. Transcriptional activity of Hnf4a in islets is restricted to the distal P2 promoter through its open chromatin configuration and an islet-specific interaction between the P2 promoter and a downstream enhancer. Exposure to suboptimal nutrition during early development leads to epigenetic silencing at the enhancer region, which weakens the P2 promoter-enhancer interaction and results in a permanent reduction in Hnf4a expression. Aging leads to progressive epigenetic silencing of the entire Hnf4a locus in islets, an effect that is more pronounced in rats exposed to a poor maternal diet. Our findings provide evidence for environmentally induced epigenetic changes at the Hnf4a enhancer that alter its interaction with the P2 promoter, and consequently determine T2D risk. We therefore propose that environmentally induced changes in promoter-enhancer interactions represent a fundamental epigenetic mechanism by which nutrition and aging can influence long-term health. [PUBLICATION ]
version8
lds50peer_reviewed
links
openurl$$Topenurl_article
openurlfulltext$$Topenurlfull_article
backlink$$Uhttp://search.proquest.com/docview/859497508/?pq-origsite=primo$$EView_record_in_ProQuest_(subscribers_only)
search
creatorcontrib
0Sandovici, Ionel
1Smith, Noel H
2Nitert, Marloes Dekker
3Ackers-Johnson, Matthew
4Uribe-Lewis, Santiago
5Ito, Yoko
6Jones, R Huw
7Marquez, Victor E
8Cairns, William
9Tadayyon, Mohammed
10O'Neill, Laura P
11Murrell, Adele
12Ling, Charlotte
13Constância, Miguel
14Ozanne, Susan E
titleMaternal diet and aging alter the epigenetic control of a promoter-enhancer interaction at the Hnf4a gene in rat pancreatic islets.
subject
0Aging–Physiology
1Animals–Genetics
2Cell Line–Cytology
3DNA Methylation–Physiology
4Diet–Physiology
5Enhancer Elements, Genetic–Physiology
6Epigenesis, Genetic–Physiology
7Female–Physiology
8Hepatocyte Nuclear Factor 4–Physiology
9Islets of Langerhans–Physiology
10Maternal Exposure–Physiology
11Promoter Regions, Genetic–Physiology
12Rats–Physiology
13Transcriptional Activation–Physiology
14Hepatocyte Nuclear Factor 4
15Hnf4a Protein, Rat
general
0English
11091-6490
210.1073/pnas.1019007108
3MEDLINE (ProQuest)
4ProQuest Biological Science Collection
5ProQuest Natural Science Collection
6ProQuest SciTech Collection
7Biological Science Database
8Natural Science Collection
9SciTech Premium Collection
10Health Research Premium Collection
11Health Research Premium Collection (Alumni edition)
sourceidproquest
recordidproquest859497508
issn
010916490
11091-6490
rsrctypearticle
creationdate2011
addtitleProceedings of the National Academy of Sciences of the United States of America
searchscope
01007527
11007944
210000004
310000038
410000050
510000120
610000159
710000238
810000253
910000260
1010000270
1110000271
1210000302
13proquest
scope
01007527
11007944
210000004
310000038
410000050
510000120
610000159
710000238
810000253
910000260
1010000270
1110000271
1210000302
13proquest
lsr43
01007527false
11007944false
210000004false
310000038false
410000050false
510000120false
610000159false
710000238false
810000253false
910000260false
1010000270false
1110000271false
1210000302false
contributorSandovici, Ionel
startdate20110329
enddate20110329
citationpf 5449 pt 5454 vol 108 issue 13
lsr30VSR-Enriched:[pqid, description, issn]
sort
titleMaternal diet and aging alter the epigenetic control of a promoter-enhancer interaction at the Hnf4a gene in rat pancreatic islets.
authorSandovici, Ionel ; Smith, Noel H ; Nitert, Marloes Dekker ; Ackers-Johnson, Matthew ; Uribe-Lewis, Santiago ; Ito, Yoko ; Jones, R Huw ; Marquez, Victor E ; Cairns, William ; Tadayyon, Mohammed ; O'Neill, Laura P ; Murrell, Adele ; Ling, Charlotte ; Constância, Miguel ; Ozanne, Susan E
creationdate20110329
lso0120110329
facets
frbrgroupid8777712984015806748
frbrtype5
newrecords20181218
languageeng
creationdate2011
topic
0Aging–Physiology
1Animals–Genetics
2Cell Line–Cytology
3DNA Methylation–Physiology
4Diet–Physiology
5Enhancer Elements, Genetic–Physiology
6Epigenesis, Genetic–Physiology
7Female–Physiology
8Hepatocyte Nuclear Factor 4–Physiology
9Islets of Langerhans–Physiology
10Maternal Exposure–Physiology
11Promoter Regions, Genetic–Physiology
12Rats–Physiology
13Transcriptional Activation–Physiology
14Hepatocyte Nuclear Factor 4
15Hnf4a Protein, Rat
collection
0MEDLINE (ProQuest)
1ProQuest Biological Science Collection
2ProQuest Natural Science Collection
3ProQuest SciTech Collection
4Biological Science Database
5Natural Science Collection
6SciTech Premium Collection
7Health Research Premium Collection
8Health Research Premium Collection (Alumni edition)
prefilterarticles
rsrctypearticles
creatorcontrib
0Sandovici, Ionel
1Smith, Noel H
2Nitert, Marloes Dekker
3Ackers-Johnson, Matthew
4Uribe-Lewis, Santiago
5Ito, Yoko
6Jones, R Huw
7Marquez, Victor E
8Cairns, William
9Tadayyon, Mohammed
10O'Neill, Laura P
11Murrell, Adele
12Ling, Charlotte
13Constância, Miguel
14Ozanne, Susan E
jtitleProceedings of the National Academy of Sciences of the United States of America
toplevelpeer_reviewed
delivery
delcategoryRemote Search Resource
fulltextfulltext
addata
aulast
0Sandovici
1Smith
2Nitert
3Ackers-Johnson
4Uribe-Lewis
5Ito
6Jones
7Marquez
8Cairns
9Tadayyon
10O'Neill
11Murrell
12Ling
13Constância
14Ozanne
aufirst
0Ionel
1Noel H
2Marloes Dekker
3Matthew
4Santiago
5Yoko
6R Huw
7Victor E
8William
9Mohammed
10Laura P
11Adele
12Charlotte
13Miguel
14Susan E
au
0Sandovici, Ionel
1Smith, Noel H
2Nitert, Marloes Dekker
3Ackers-Johnson, Matthew
4Uribe-Lewis, Santiago
5Ito, Yoko
6Jones, R Huw
7Marquez, Victor E
8Cairns, William
9Tadayyon, Mohammed
10O'Neill, Laura P
11Murrell, Adele
12Ling, Charlotte
13Constância, Miguel
14Ozanne, Susan E
addauSandovici, Ionel
atitleMaternal diet and aging alter the epigenetic control of a promoter-enhancer interaction at the Hnf4a gene in rat pancreatic islets.
jtitleProceedings of the National Academy of Sciences of the United States of America
risdate20110329
volume108
issue13
spage5449
epage5454
pages5449-5454
eissn1091-6490
formatjournal
genrearticle
ristypeJOUR
doi10.1073/pnas.1019007108
urlhttp://search.proquest.com/docview/859497508/
issn00278424
date2011-03-29