Deprecated: Implicit conversion from float 233.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534
Deprecated: Implicit conversion from float 233.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534
Deprecated: Implicit conversion from float 233.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534
Deprecated: Implicit conversion from float 233.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534
Deprecated: Implicit conversion from float 233.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534
Deprecated: Implicit conversion from float 233.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534
Deprecated: Implicit conversion from float 233.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534
Deprecated: Implicit conversion from float 267.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534
Deprecated: Implicit conversion from float 267.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534
Deprecated: Implicit conversion from float 267.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534
Deprecated: Implicit conversion from float 267.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534
Warning: imagejpeg(C:\Inetpub\vhosts\kidney.de\httpdocs\phplern\27831498
.jpg): Failed to open stream: No such file or directory in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 117 Genome+Res
2017 ; 27
(1
): 38-52
Nephropedia Template TP
gab.com Text
Twit Text FOAVip
Twit Text #
English Wikipedia
A systematic comparison reveals substantial differences in chromosomal versus
episomal encoding of enhancer activity
#MMPMID27831498
Inoue F
; Kircher M
; Martin B
; Cooper GM
; Witten DM
; McManus MT
; Ahituv N
; Shendure J
Genome Res
2017[Jan]; 27
(1
): 38-52
PMID27831498
show ga
Candidate enhancers can be identified on the basis of chromatin modifications,
the binding of chromatin modifiers and transcription factors and cofactors, or
chromatin accessibility. However, validating such candidates as bona fide
enhancers requires functional characterization, typically achieved through
reporter assays that test whether a sequence can increase expression of a
transcriptional reporter via a minimal promoter. A longstanding concern is that
reporter assays are mainly implemented on episomes, which are thought to lack
physiological chromatin. However, the magnitude and determinants of differences
in cis-regulation for regulatory sequences residing in episomes versus
chromosomes remain almost completely unknown. To address this systematically, we
developed and applied a novel lentivirus-based massively parallel reporter assay
(lentiMPRA) to directly compare the functional activities of 2236 candidate liver
enhancers in an episomal versus a chromosomally integrated context. We find that
the activities of chromosomally integrated sequences are substantially different
from the activities of the identical sequences assayed on episomes, and
furthermore are correlated with different subsets of ENCODE annotations. The
results of chromosomally based reporter assays are also more reproducible and
more strongly predictable by both ENCODE annotations and sequence-based models.
With a linear model that combines chromatin annotations and sequence information,
we achieve a Pearson's R(2) of 0.362 for predicting the results of chromosomally
integrated reporter assays. This level of prediction is better than with either
chromatin annotations or sequence information alone and also outperforms
predictive models of episomal assays. Our results have broad implications for how
cis-regulatory elements are identified, prioritized and functionally validated.
|Chromatin Assembly and Disassembly/genetics
[MESH]