Building the heart piece by piece: modularity of cis-elements regulating Nkx2-5 transcription

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.

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 ◽  
...  

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.


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.


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

Development ◽  
1991 ◽  
Vol 112 (3) ◽  
pp. 807-811 ◽  
Author(s):  
K. Schughart ◽  
C.J. Bieberich ◽  
R. Eid ◽  
F.H. Ruddle

To characterize cis-acting regulatory elements of the murine homeobox gene, Hox-2.2, transgenic mouse lines were generated that contained the LacZ reporter gene under the control of different fragments from the presumptive Hox-2.2 promoter. A promoter region of 3600 base pairs (bp) was identified, which reproducibly directed reporter gene expression into specific regions of developing mouse embryos. At 8.5 days postcoitum (p.c.) reporter gene activity was detected in posterior regions of the lateral mesoderm and, in subsequent developmental stages, expression of the LacZ gene was restricted to specific regions of the developing limb buds and the mesenchyme of the ventrolateral body region. This pattern of Hox-2.2-LacZ expression was found in all transgenic embryos that have been generated with the 3.6 kb promoter fragment (two founder embryos and embryos from five transgenic lines). In addition, embryos from two transgenic mouse lines expressed the reporter gene at low levels in the developing central nervous system (CNS). Our results are consistent with the idea that in addition to their presumptive role in CNS and vertebrae development, Hox-2.2 gene products are involved in controlling pattern formation in developing limbs.


2019 ◽  
Vol 19 (1) ◽  
Author(s):  
Lin Zhang ◽  
Zhiqiang Song ◽  
Fangfang Li ◽  
Xixi Li ◽  
Haikun Ji ◽  
...  

Abstract Background Drought stress is one of the major abiotic stresses that affects plant growth and productivity. The GAPCp genes play important roles in drought stress tolerance in multiple species. The aim of this experiment was to identify the core cis-regulatory elements that may respond to drought stress in the GAPCp2 and GAPCp3 promoter sequences. Results In this study, the promoters of GAPCp2 and GAPCp3 were cloned. The promoter activities were significantly improved under abiotic stress via regulation of Rluc reporter gene expression, while promoter sequence analysis indicated that these fragments were not almost identical. In transgenic Arabidopsis with the expression of the GUS reporter gene under the control of one of these promoters, the activities of GUS were strong in almost all tissues except the seeds, and the activities were induced after abiotic stress. The yeast one-hybrid system and EMSA demonstrated that TaMYB bound TaGAPCp2P/3P. By analyzing different 5′ deletion mutants of these promoters, it was determined that TaGAPCp2P (− 1312~ − 528) and TaGAPCp3P (− 2049~ − 610), including the MYB binding site, contained enhancer elements that increased gene expression levels under drought stress. We used an effector and a reporter to co-transform tobacco and found that TaMYB interacted with the specific MYB binding sites of TaGAPCp2P (− 1197~ − 635) and TaGAPCp3P (− 1456~ − 1144 and − 718~ − 610) in plant cells. Then, the Y1H system and EMSA assay demonstrated that these MYB binding sites in TaGAPCp2P (− 1135 and − 985) and TaGAPCp3P (− 1414 and − 665) were the target cis-elements of TaMYB. The deletion of the specific MYB binding sites in the promoter fragments significantly restrained the drought response, and these results confirmed that these MYB binding sites (AACTAAA/C) play vital roles in improving the transcription levels under drought stress. The results of qRT-PCR in wheat protoplasts transiently overexpressing TaMYB indicated that the expression of TaGAPCp2/3 induced by abiotic stress was upregulated by TaMYB. Conclusion The MYB binding sites (AACTAAA/C) in TaGAPCp2P/3P were identified as the key cis-elements for responding to drought stress and were bound by the transcription factor TaMYB.


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