Promoter-enhancer looping and shadow enhancers of the mouse αA-crystallin locus

Rebecca S. McGreal-Estrada, Louise V. Wolf, Ales Cvekl

Research output: Contribution to journalArticle

Abstract

Gene regulation by enhancers is important for precise temporal and spatial gene expression. Enhancers can drive gene expression regardless of their location, orientation or distance from the promoter. Changes in chromatin conformation and chromatin looping occur to bring the promoter and enhancers into close proximity. αA-crystallin ranks among one of the most abundantly expressed genes and proteins in the mammalian lens. The αA-crystallin locus is characterized by a 16 kb chromatin domain marked by two distal enhancers, 5′ DCR1 and 3′ DCR3. Here we used chromatin conformation capture (3C) analysis and transgenic approaches to analyze temporal control of the mouse αA-crystallin gene. We find that DCR1 is necessary, but not sufficient alone to drive expression at E10.5 in the mouse lens pit. Chromatin looping revealed interaction between the promoter and the region 3′ to DCR1, identifying a novel enhancer region in the αA-crystallin locus. We determined that this novel enhancer region, DCR1S, recapitulates the temporal control by DCR1. Acting as shadow enhancers, DCR1 and DCR1S are able to control expression in the lens vesicle at E11.5. It remains to be elucidated however, which region of the αA-crystallin locus is responsible for expression in the lens pit at E10.5.

Original languageEnglish (US)
Article numberbio036897
JournalBiology Open
Volume7
Issue number12
DOIs
StatePublished - Jan 1 2018

Fingerprint

crystallins
Crystallins
Chromatin
chromatin
Lens
promoter regions
Lenses
loci
Gene expression
mice
Conformations
Gene Expression
gene expression
genes
Genetic Promoter Regions
Genes
genetically modified organisms
Proteins
proteins

Keywords

  • Chromatin looping
  • Development
  • Enhancer
  • Lens
  • Shadow enhancer
  • αA-crystallin

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)

Cite this

Promoter-enhancer looping and shadow enhancers of the mouse αA-crystallin locus. / McGreal-Estrada, Rebecca S.; Wolf, Louise V.; Cvekl, Ales.

In: Biology Open, Vol. 7, No. 12, bio036897, 01.01.2018.

Research output: Contribution to journalArticle

McGreal-Estrada, Rebecca S. ; Wolf, Louise V. ; Cvekl, Ales. / Promoter-enhancer looping and shadow enhancers of the mouse αA-crystallin locus. In: Biology Open. 2018 ; Vol. 7, No. 12.
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