Transcriptional enhancers in protein-coding exons of vertebrate developmental genes.

PloS One
Deborah RitterJeffrey H Chuang

Abstract

Many conserved noncoding sequences function as transcriptional enhancers that regulate gene expression. Here, we report that protein-coding DNA also frequently contains enhancers functioning at the transcriptional level. We tested the enhancer activity of 31 protein-coding exons, which we chose based on strong sequence conservation between zebrafish and human, and occurrence in developmental genes, using a Tol2 transposable GFP reporter assay in zebrafish. For each exon we measured GFP expression in hundreds of embryos in 10 anatomies via a novel system that implements the voice-recognition capabilities of a cellular phone. We find that 24/31 (77%) exons drive GFP expression compared to a minimal promoter control, and 14/24 are anatomy-specific (expression in four anatomies or less). GFP expression driven by these coding enhancers frequently overlaps the anatomies where the host gene is expressed (60%), suggesting self-regulation. Highly conserved coding sequences and highly conserved noncoding sequences do not significantly differ in enhancer activity (coding: 24/31 vs. noncoding: 105/147) or tissue-specificity (coding: 14/24 vs. noncoding: 50/105). Furthermore, coding and noncoding enhancers display similar levels of the enha...Continue Reading

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Citations

Oct 25, 2013·Briefings in Functional Genomics·Marco FergUwe Strähle
Dec 18, 2013·Science·Andrew B StergachisJohn A Stamatoyannopoulos
Jan 15, 2013·Plant Physiology·Fangfang Wang, Sharyn E Perry
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Oct 27, 2015·Molecular Biology and Evolution·Rachel M Agoglia, Hunter B Fraser
Dec 5, 2014·Genome Medicine·Ken J KronMathieu Lupien
Nov 6, 2012·Biochimica Et Biophysica Acta·Judith Marsman, Julia A Horsfield
Feb 27, 2015·Cellular and Molecular Life Sciences : CMLS·Maksim ErokhinDarya Chetverina
Nov 2, 2014·PloS One·Longquan QuanLiangxue Lai
Jun 30, 2016·Human Molecular Genetics·Anton A Komar
Feb 7, 2017·Nature Reviews. Genetics·Florence PetitNadav Ahituv
Feb 17, 2017·Molecular Biology and Evolution·Parul JohriMichael Lynch
May 10, 2017·Journal of Lipid Research·Christopher M AllanStephen G Young
Mar 31, 2018·Frontiers in Neuroscience·Ugo BorelloColette Dehay
Dec 13, 2018·Genome Biology·Abigail F GroffJohn L Rinn
Mar 24, 2012·Genome Research·Ramon Y BirnbaumNadav Ahituv

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Methods Mentioned

BETA
transgenic
ChIP-seq
sequence-based prediction
ChIP

Software Mentioned

BedTools
Fasta Genome Browser
Refseq
Ensembl
PERL script
DragonDictation
Dragon Dictation
BedTools IntersectBed
R Statistical package
IntersectBed

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