scholarly journals Integrated omics networks reveal the temporal signaling events of brassinosteroid response in Arabidopsis

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Natalie M. Clark ◽  
Trevor M. Nolan ◽  
Ping Wang ◽  
Gaoyuan Song ◽  
Christian Montes ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Cell Division ◽  
Network Inference ◽  
Phosphorylation Sites ◽  
Molecular Signaling ◽  
Signaling Events ◽  
Spatiotemporal Clustering ◽  
Integrated Omics ◽  
Omic Data ◽  
Integrative Network

AbstractBrassinosteroids (BRs) are plant steroid hormones that regulate cell division and stress response. Here we use a systems biology approach to integrate multi-omic datasets and unravel the molecular signaling events of BR response in Arabidopsis. We profile the levels of 26,669 transcripts, 9,533 protein groups, and 26,617 phosphorylation sites from Arabidopsis seedlings treated with brassinolide (BL) for six different lengths of time. We then construct a network inference pipeline called Spatiotemporal Clustering and Inference of Omics Networks (SC-ION) to integrate these data. We use our network predictions to identify putative phosphorylation sites on BES1 and experimentally validate their importance. Additionally, we identify BRONTOSAURUS (BRON) as a transcription factor that regulates cell division, and we show that BRON expression is modulated by BR-responsive kinases and transcription factors. This work demonstrates the power of integrative network analysis applied to multi-omic data and provides fundamental insights into the molecular signaling events occurring during BR response.

scholarly journals Integrated omics networks reveal the temporal signaling events of brassinosteroid response in Arabidopsis

2020 ◽  
Author(s):  
Natalie M Clark ◽  
Trevor M Nolan ◽  
Ping Wang ◽  
Gaoyuan Song ◽  
Christian Montes ◽  
...  
Keyword(s):  
Cell Division ◽  
Network Inference ◽  
Phosphorylation Sites ◽  
Molecular Signaling ◽  
Kinase Substrate ◽  
Signaling Events ◽  
Spatiotemporal Clustering ◽  
Integrated Omics ◽  
Substrate Phosphorylation ◽  
Integrative Network

Brassinosteroids (BRs) are plant steroid hormones that are known to regulate cell division and stress response. We used a systems biology approach to integrate multi-omic datasets and unravel the molecular signaling events of BR response in Arabidopsis. We profiled the levels of 32,549 transcripts, 9,035 protein groups, and 26,950 phosphorylation sites from Arabidopsis seedlings treated with brassinolide (BL, most active BR) for six different lengths of time. We then constructed a network inference pipeline called Spatiotemporal Clustering and Inference of Omics Networks (SC-ION) that was able to integrate these multi-omic data into one, cohesive regulatory network. Our network illustrates the signaling cascade of BR response, starting with kinase-substrate phosphorylation and ending with transcriptional regulation. We used our network predictions to identify putative, relevant phosphorylation sites on the TF BRI1-EMS-SUPPRESSOR 1 (BES1); the importance of which we experimentally validated. Additionally, we identified an uncharacterized TF, which we named BRONTOSAURUS (BRON), that regulates cell division. Further, we show that bron mutant roots are hypersensitive to BL. Together, this work demonstrates the power of integrative network analysis applied to multiomic data and provides fundamental insights into the molecular signaling events occurring during BR response.

scholarly journals The EGL-13 SOX Domain Transcription Factor Affects the Uterine Cell Lineages in Caenorhabditis elegans

Genetics ◽  
2003 ◽  
Vol 165 (3) ◽  
pp. 1623-1628
Author(s):  
Hediye Nese Cinar ◽  
Keri L Richards ◽  
Kavita S Oommen ◽  
Anna P Newman
Keyword(s):  
Transcription Factor ◽  
Cell Division ◽  
Caenorhabditis Elegans ◽  
Cell Fate ◽  
Cell Lineages

Abstract We isolated egl-13 mutants in which the cells of the Caenorhabditis elegans uterus initially appeared to develop normally but then underwent an extra round of cell division. The data suggest that egl-13 is required for maintenance of the cell fate.

The BES1/BZR1-family transcription factor MpBES1 regulates cell division and differentiation in Marchantia polymorpha

2021 ◽  
Author(s):  
Martin A. Mecchia ◽  
Mariano García-Hourquet ◽  
Fidel Lozano-Elena ◽  
Ainoa Planas-Riverola ◽  
David Blasco-Escamez ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Cell Division ◽  
Marchantia Polymorpha

scholarly journals Balancing dynamic tradeoffs drives cellular reprogramming

2018 ◽  
Author(s):  
Kimberley N. Babos ◽  
Kate E. Galloway ◽  
Kassandra Kisler ◽  
Madison Zitting ◽  
Yichen Li ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Cell Division ◽  
Motor Neuron ◽  
Molecular Mechanisms ◽  
Cell Types ◽  
Cellular Reprogramming ◽  
Cellular Event ◽  
Chemical Factors ◽  
Number Of Cells ◽  
Transcription And Replication

AbstractAlthough cellular reprogramming continues to generate new cell types, reprogramming remains a rare cellular event. The molecular mechanisms that limit reprogramming, particularly to somatic lineages, remain unclear. By examining fibroblast-to-motor neuron conversion, we identify a previously unappreciated dynamic between transcription and replication that determines reprogramming competency. Transcription factor overexpression forces most cells into states that are refractory to reprogramming and are characterized by either hypertranscription with little cell division, or hyperproliferation with low transcription. We identify genetic and chemical factors that dramatically increase the number of cells capable of both hypertranscription and hyperproliferation. Hypertranscribing, hyperproliferating cells reprogram at 100-fold higher, near-deterministic rates. We demonstrate that elevated topoisomerase expression endows cells with privileged reprogramming capacity, suggesting that biophysical constraints limit cellular reprogramming to rare events.

On the Synchrony of Morphological and Molecular Signaling Events in Cell Migration

2009 ◽  
pp. 469-477
Author(s):  
Justin Dauwels ◽  
Yuki Tsukada ◽  
Yuichi Sakumura ◽  
Shin Ishii ◽  
Kazuhiro Aoki ◽  
...  
Keyword(s):  
Cell Migration ◽  
Molecular Signaling ◽  
Signaling Events

scholarly journals Co-regulation of the transcription controlling ATF2 phosphoswitch by JNK and p38

2020 ◽  
Vol 11 (1) ◽  
Author(s):  
Klára Kirsch ◽  
András Zeke ◽  
Orsolya Tőke ◽  
Péter Sok ◽  
Ashish Sethi ◽  
...  
Keyword(s):  
Gene Expression ◽  
Transcription Factor ◽  
Binding Sites ◽  
Mechanistic Modeling ◽  
Environmental Cues ◽  
Phosphorylation Sites ◽  
Binding Motifs ◽  
Mitogen Activated Protein Kinases ◽  
Transactivation Domains ◽  
Mitogen Activated Protein

AbstractTranscription factor phosphorylation at specific sites often activates gene expression, but how environmental cues quantitatively control transcription is not well-understood. Activating protein 1 transcription factors are phosphorylated by mitogen-activated protein kinases (MAPK) in their transactivation domains (TAD) at so-called phosphoswitches, which are a hallmark in response to growth factors, cytokines or stress. We show that the ATF2 TAD is controlled by functionally distinct signaling pathways (JNK and p38) through structurally different MAPK binding sites. Moreover, JNK mediated phosphorylation at an evolutionarily more recent site diminishes p38 binding and made the phosphoswitch differently sensitive to JNK and p38 in vertebrates. Structures of MAPK-TAD complexes and mechanistic modeling of ATF2 TAD phosphorylation in cells suggest that kinase binding motifs and phosphorylation sites line up to maximize MAPK based co-regulation. This study shows how the activity of an ancient transcription controlling phosphoswitch became dependent on the relative flux of upstream signals.

scholarly journals Leukemia-Related Transcription Factor TEL Is Negatively Regulated through Extracellular Signal-Regulated Kinase-Induced Phosphorylation

2004 ◽  
Vol 24 (8) ◽  
pp. 3227-3237 ◽  
Author(s):  
Kazuhiro Maki ◽  
Honoka Arai ◽  
Kazuo Waga ◽  
Ko Sasaki ◽  
Fumihiko Nakamura ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Dna Binding ◽  
Dominant Negative ◽  
Mitogen Activated Protein Kinase ◽  
Dominant Negative Effect ◽  
Phosphorylation Sites ◽  
3T3 Cells ◽  
Nih 3T3 ◽  
Nih 3T3 Cells

ABSTRACT TEL is an ETS family transcription factor that possesses multiple putative mitogen-activated protein kinase phosphorylation sites. We here describe the functional regulation of TEL via ERK pathways. Overexpressed TEL becomes phosphorylated in vivo by activated ERK. TEL is also directly phosphorylated in vitro by ERK. The inducible phosphorylation sites are Ser213 and Ser257. TEL binds to a common docking domain in ERK. In vivo ERK-dependent phosphorylation reduces trans-repressional and DNA-binding abilities of TEL for ETS-binding sites. A mutant carrying substituted glutamates on both Ser213 and Ser257 functionally mimics hyperphosphorylated TEL and also shows a dominant-negative effect on TEL-induced transcriptional suppression. Losing DNA-binding affinity through phosphorylation but heterodimerizing with unmodified TEL could be an underlying mechanism. Moreover, the glutamate mutant dominantly interferes with TEL-induced erythroid differentiation in MEL cells and growth suppression in NIH 3T3 cells. Finally, endogenous TEL is dephosphorylated in parallel with ERK inactivation in differentiating MEL cells and is phosphorylated through ERK activation in Ras-transformed NIH 3T3 cells. These data indicate that TEL is a constituent downstream of ERK in signal transduction systems and is physiologically regulated by ERK in molecular and biological features.

scholarly journals Retroelement—Linked Transcription Factor Binding Patterns Point to Quickly Developing Molecular Pathways in Human Evolution

Cells ◽  
2019 ◽  
Vol 8 (2) ◽  
pp. 130 ◽  
Author(s):  
Daniil Nikitin ◽  
Andrew Garazha ◽  
Maxim Sorokin ◽  
Dmitry Penzar ◽  
Victor Tkachev ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Transcriptional Regulation ◽  
Transcription Factor Binding ◽  
Molecular Pathways ◽  
Molecular Signaling ◽  
Regulatory Evolution ◽  
Factor Binding ◽  
Human Genes ◽  
Fatty Acids Metabolism ◽  
Cellular Immune

Background: Retroelements (REs) are transposable elements occupying ~40% of the human genome that can regulate genes by providing transcription factor binding sites (TFBS). RE-linked TFBS profile can serve as a marker of gene transcriptional regulation evolution. This approach allows for interrogating the regulatory evolution of organisms with RE-rich genomes. We aimed to characterize the evolution of transcriptional regulation for human genes and molecular pathways using RE-linked TFBS accumulation as a metric. Methods: We characterized human genes and molecular pathways either enriched or deficient in RE-linked TFBS regulation. We used ENCODE database with mapped TFBS for 563 transcription factors in 13 human cell lines. For 24,389 genes and 3124 molecular pathways, we calculated the score of RE-linked TFBS regulation reflecting the regulatory evolution rate at the level of individual genes and molecular pathways. Results: The major groups enriched by RE regulation deal with gene regulation by microRNAs, olfaction, color vision, fertilization, cellular immune response, and amino acids and fatty acids metabolism and detoxication. The deficient groups were involved in translation, RNA transcription and processing, chromatin organization, and molecular signaling. Conclusion: We identified genes and molecular processes that have characteristics of especially high or low evolutionary rates at the level of RE-linked TFBS regulation in human lineage.

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