scholarly journals Discovery of gene regulatory elements through a new bioinformatics analysis of haploid genetic screens

2018 ◽  
Author(s):  
Bhaven B. Patel ◽  
Andres M. Lebensohn ◽  
Jan E. Carette ◽  
Julia Salzman ◽  
Rajat Rohatgi

AbstractThe systematic identification of regulatory elements that control gene expression remains a challenge. Genetic screens that use untargeted mutagenesis have the potential to identify protein-coding genes, non-coding RNAs and regulatory elements, but their analysis has mainly focused on identifying the former two. To identify regulatory elements, we conducted a new bioinformatics analysis of insertional mutagenesis screens interrogating WNT signaling in haploid human cells. We searched for specific patterns of retroviral gene trap integrations (used as mutagens in haploid screens) in short genomic intervals overlapping with introns and regions upstream of genes. We uncovered atypical patterns of gene trap insertions that were not predicted to disrupt coding sequences, but caused changes in the expression of two key regulators of WNT signaling, suggesting the presence of cis-regulatory elements. Our methodology extends the scope of haploid genetic screens by enabling the identification of regulatory elements that control gene expression.

2016 ◽  
Vol 127 (2) ◽  
pp. 269-287 ◽  
Author(s):  
Róża Biłas ◽  
Katarzyna Szafran ◽  
Katarzyna Hnatuszko-Konka ◽  
Andrzej K. Kononowicz

2018 ◽  
Vol 72 (5) ◽  
pp. 862-874.e5 ◽  
Author(s):  
Orel Mizrahi ◽  
Aharon Nachshon ◽  
Alina Shitrit ◽  
Idit A. Gelbart ◽  
Martina Dobesova ◽  
...  

2021 ◽  
Author(s):  
Nicolle A. Bonar ◽  
David I. Gittin ◽  
Christian P. Petersen

Tissue identity determination is critical for regeneration, and the planarian anteroposterior (AP) axis uses positional control genes expressed from bodywall muscle to determine body regionalization. Canonical Wnt signaling establishes anterior versus posterior pole identities through notum and wnt1 signaling, and two Wnt/FGFRL signaling pathways control head and trunk domains, but their downstream signaling mechanisms are not fully understood. Here we identify a planarian Src homolog that restricts head and trunk identities to anterior positions. src-1(RNAi) animals formed enlarged brains and ectopic eyes and also duplicated trunk tissue, similar to a combination of Wnt/FGFRL RNAi phenotypes. src-1 was required for establishing territories of positional control gene expression, indicating it acts at an upstream step in patterning the AP axis. Double RNAi experiments and eye regeneration assays suggest src-1 can act in parallel to at least some Wnt and FGFRL factors. Co-inhibition of src-1 with other posterior-promoting factors led to dramatic patterning changes and a reprogramming of Wnt/FGFRLs into controlling new positional outputs. These results identify src-1 as a factor that promotes robustness of the AP positional system that instructs appropriate regeneration.


Development ◽  
1999 ◽  
Vol 126 (19) ◽  
pp. 4187-4192 ◽  
Author(s):  
R.J. Schwartz ◽  
E.N. Olson

Heart formation in Drosophila is dependent on the homeobox gene tinman. The homeobox gene Nkx2-5 is closely related to tinman and is the earliest known marker for cardiogenesis in vertebrate embryos. Recent studies of cis-regulatory elements required for Nkx2-5 expression in the developing mouse heart have revealed an extraordinary array of independent cardiac enhancers, and associated negative regulatory elements, that direct transcription in distinct regions of the embryonic heart. These studies demonstrate the modularity in cardiac transcription, in which different regulatory elements respond to distinct sets of transcription factors to control gene expression in different compartments of the developing heart. We consider the potential mechanisms underlying such transcriptional complexity, its possible significance for cardiac function, and the implications for evolution of the multichambered heart.


2010 ◽  
Vol 82 (4) ◽  
pp. 933-939 ◽  
Author(s):  
John S. Mattick

Notwithstanding lineage-specific variations, the number and type of protein-coding genes remain relatively static across the animal kingdom. By contrast there has been a massive expansion in the extent of genomic non-proteincoding sequences with increasing developmental complexity. These non-coding sequences are, in fact, transcribed in a regulated manner to produce large numbers of large and small non-protein-coding RNAs that control gene expression at many levels including chromatin architecture, post-transcriptional processing and translation. Moreover, many RNAs are edited, especially in the nervous system, which may be the basis of epigenome-environment interactions and the function of the brain.


2019 ◽  
Author(s):  
Claudia Racioppi ◽  
Keira A Wiechecki ◽  
Lionel Christiaen

ABSTRACTIn embryos, lineage-specific profiles of chromatin accessibility control gene expression by modulating transcription, and thus impact multipotent progenitor states and subsequent fate choices. Subsets of cardiac and pharyngeal/head muscles share a common origin in the cardiopharyngeal mesoderm, but the chromatin landscapes that govern multipotent progenitors’ competence and early fate choices remain largely elusive. Here, we leveraged the simplicity of the chordate model Ciona to profile chromatin accessibility through stereotyped transitions from naive Mesp+ mesoderm to distinct fate-restricted heart and pharyngeal muscle precursors. An FGF-Foxf pathway acts in multipotent progenitors to establish cardiopharyngeal-specific patterns of accessibility, which govern later heart vs. pharyngeal muscle-specific expression profiles, demonstrating extensive spatiotemporal decoupling between early cardiopharyngeal enhancer accessibility and late cell-type-specific activity. Combinations of cis-regulatory elements with distinct chromatin accessibility profiles are required to activate of Ebf and Tbx1/10, two key determinants of cardiopharyngeal fate choices. We propose that this higher order combinatorial logic increases the repertoire of regulatory inputs that control gene expression, through either accessibility and/or activity, thus fostering spatially and temporally accurate fate choices.


2009 ◽  
Vol 185 (5) ◽  
pp. 761-763 ◽  
Author(s):  
Valerie Horsley

Stem cells use both transcriptional and epigenetic mechanisms to control gene expression and regulate tissue development and homeostasis. In this issue, Gu et al. (Gu, B., P. Sun, Y. Yuan, R.C. Moraes, A. Li, A. Teng, A. Agrawal, C. Rhéaume, V. Bilanchone, J.M. Veltmaat, et al. 2009. J. Cell Biol. 185:811–826) reveal an important link between these two mechanisms in mammary epithelial stem cells by showing that transcriptional activation of β-catenin downstream of Wnt signaling can be regulated epigenetically through a chromatin remodeling factor, Pygo2.


Author(s):  
C. Boulard ◽  
J. Thévenin ◽  
O. Tranquet ◽  
V. Laporte ◽  
L. Lepiniec ◽  
...  

1974 ◽  
Vol 71 (12) ◽  
pp. 5057-5061 ◽  
Author(s):  
T. Barrett ◽  
D. Maryanka ◽  
P. H. Hamlyn ◽  
H. J. Gould

2021 ◽  
Vol 120 (3) ◽  
pp. 354a
Author(s):  
Anand P. Singh ◽  
Ping Wu ◽  
Eric F. Wieschaus ◽  
Jared E. Toettcher ◽  
Thomas Gregor

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