scholarly journals Function of cofactor Akirin2 in the regulation of gene expression in model human Caucasian neutrophil-like HL60 cells

2021 ◽  
Vol 41 (7) ◽  
Author(s):  
Sara Artigas-Jerónimo ◽  
Margarita Villar ◽  
Agustín Estrada-Peña ◽  
Adrián Velázquez-Campoy ◽  
Pilar Alberdi ◽  
...  

Abstract The Akirin family of transcription cofactors are involved throughout the metazoan in the regulation of different biological processes (BPs) such as immunity, interdigital regression, muscle and neural development. Akirin do not have catalytic or DNA-binding capability and exert its regulatory function primarily through interacting proteins such as transcription factors, chromatin remodelers, and RNA-associated proteins. In the present study, we focused on the human Akirin2 regulome and interactome in neutrophil-like model human Caucasian promyelocytic leukemia HL60 cells. Our hypothesis is that metazoan evolved to have Akirin2 functional complements and different Akirin2-mediated mechanisms for the regulation of gene expression. To address this hypothesis, experiments were conducted using transcriptomics, proteomics and systems biology approaches in akirin2 knockdown and wildtype (WT) HL60 cells to characterize Akirin2 gene/protein targets, functional complements and to provide evidence of different mechanisms that may be involved in Akirin2-mediated regulation of gene expression. The results revealed Akirin2 gene/protein targets in multiple BPs with higher representation of immunity and identified immune response genes as candidate Akirin2 functional complements. In addition to linking chromatin remodelers with transcriptional activation, Akirin2 also interacts with histone H3.1 for regulation of gene expression.

2021 ◽  
Author(s):  
Sara Artigas-Jerónimo ◽  
Margarita Villar ◽  
Agustín Estrada-Peña ◽  
Adrián Velázquez-Campoy ◽  
Pilar Alberdi ◽  
...  

The Akirin family of transcription cofactors are involved throughout the metazoan in the regulation of different biological processes such as immunity, interdigital regression, muscle and neural development. Akirin do not have catalytic or DNA-binding capability and exert its regulatory function primarily through interacting proteins such as transcription factors, chromatin remodelers, and RNA-associated proteins. In this study, we focused on the human Akirin2 regulome and interactome in neutrophil-like model human Caucasian promyelocytic leukemia HL60 cells. Our hypothesis is that metazoan evolved to have Akirin2 functional complements and different Akirin2-mediated mechanisms for the regulation of gene expression. To address this hypothesis, experiments were conducted using transcriptomics, proteomics and systems biology approaches in akirin2 knockdown and wildtype HL60 cells to characterize Akirin2 gene/protein targets, functional complements and to provide evidence of different mechanisms that may be involved in Akirin2-mediated regulation of gene expression. The results revealed Akirin2 gene/protein targets in multiple biological processes with higher representation of immunity and identified immune response genes as candidate Akirin2 functional complements. In addition to linking chromatin remodelers with transcriptional activation, Akirin2 also interacts with histone H3.1 for regulation of gene expression.


2007 ◽  
Vol 282 (49) ◽  
pp. 35449-35456 ◽  
Author(s):  
Hiroko Morimoto ◽  
Kunio Kondoh ◽  
Satoko Nishimoto ◽  
Kazuya Terasawa ◽  
Eisuke Nishida

ERK5 plays a crucial role in many biological processes by regulating transcription. ERK5 has a large C-terminal-half that contains a transcriptional activation domain. However, it has remained unclear how its transcriptional activation activity is regulated. Here, we show that the activated kinase activity of ERK5 is required for the C-terminal-half to enhance the AP-1 activity, and that the activated ERK5 undergoes autophosphorylation on its most C-terminal region. Changing these phosphorylatable threonine and serine residues to unphosphorylatable alanines significantly reduces the transcriptional activation activity of ERK5. Moreover, phosphomimetic mutants of the C-terminal-half of ERK5 without an N-terminal kinase domain are shown to be able to enhance the AP-1 activity in fibroblastic cells. These results reveal the role of the stimulus-induced ERK5 autophosphorylation in regulation of gene expression.


2019 ◽  
Vol 23 (15) ◽  
pp. 1663-1670 ◽  
Author(s):  
Chunyan Ao ◽  
Shunshan Jin ◽  
Yuan Lin ◽  
Quan Zou

Protein methylation is an important and reversible post-translational modification that regulates many biological processes in cells. It occurs mainly on lysine and arginine residues and involves many important biological processes, including transcriptional activity, signal transduction, and the regulation of gene expression. Protein methylation and its regulatory enzymes are related to a variety of human diseases, so improved identification of methylation sites is useful for designing drugs for a variety of related diseases. In this review, we systematically summarize and analyze the tools used for the prediction of protein methylation sites on arginine and lysine residues over the last decade.


2021 ◽  
Vol 22 (2) ◽  
pp. 522
Author(s):  
Noreen Falak ◽  
Qari Muhammad Imran ◽  
Adil Hussain ◽  
Byung-Wook Yun

Plants are in continuous conflict with the environmental constraints and their sessile nature demands a fine-tuned, well-designed defense mechanism that can cope with a multitude of biotic and abiotic assaults. Therefore, plants have developed innate immunity, R-gene-mediated resistance, and systemic acquired resistance to ensure their survival. Transcription factors (TFs) are among the most important genetic components for the regulation of gene expression and several other biological processes. They bind to specific sequences in the DNA called transcription factor binding sites (TFBSs) that are present in the regulatory regions of genes. Depending on the environmental conditions, TFs can either enhance or suppress transcriptional processes. In the last couple of decades, nitric oxide (NO) emerged as a crucial molecule for signaling and regulating biological processes. Here, we have overviewed the plant defense system, the role of TFs in mediating the defense response, and that how NO can manipulate transcriptional changes including direct post-translational modifications of TFs. We also propose that NO might regulate gene expression by regulating the recruitment of RNA polymerase during transcription.


Cells ◽  
2020 ◽  
Vol 9 (10) ◽  
pp. 2152
Author(s):  
Robin Loesch ◽  
Linda Chenane ◽  
Sabine Colnot

Chromatin remodelers are found highly mutated in cancer including hepatocellular carcinoma. These mutations frequently occur in ARID (AT-rich Interactive Domain) genes, encoding subunits of the ATP-dependent SWI/SNF remodelers. The increasingly prevalent complexity that surrounds the functions and specificities of the highly modular BAF (BG1/BRM-associated factors) and PBAF (polybromo-associated BAF) complexes, including ARID1A/B or ARID2, is baffling. The involvement of the SWI/SNF complexes in diverse tissues and processes, and especially in the regulation of gene expression, multiplies the specific outcomes of specific gene alterations. A better understanding of the molecular consequences of specific mutations impairing chromatin remodelers is needed. In this review, we summarize what we know about the tumor-modulating properties of ARID2 in hepatocellular carcinoma.


1990 ◽  
Vol 10 (10) ◽  
pp. 5532-5535 ◽  
Author(s):  
C Abate ◽  
D Luk ◽  
E Gagne ◽  
R G Roeder ◽  
T Curran

The products of c-fos and c-jun (Fos and Jun) function in gene regulation by interacting with the AP-1 binding site. Here we have examined the contribution of Fos and Jun toward transcriptional activity by using Fos and Jun polypeptides purified from Escherichia coli. Fos contained a transcriptional activation domain as well as a region which exerted a negative influence on transcriptional activity in vitro. Moreover, distinct activation domains in both Fos and Jun functioned cooperatively in transcriptional stimulation. Thus, regulation of gene expression by Fos and Jun results from an integration of several functional domains in a bimolecular complex.


2018 ◽  
Vol 24 (5) ◽  
pp. 471-485 ◽  
Author(s):  
Jillian Belgrad ◽  
R. Douglas Fields

The temporal coding of action potential activity is fundamental to nervous system function. Here we consider how gene expression in neurons is regulated by specific patterns of action potential firing, with an emphasis on new information on epigenetic regulation of gene expression. Patterned action potential activity activates intracellular signaling networks selectively in accordance with the kinetics of activation and inactivation of second messengers, phosphorylation and dephosphorylation of protein kinases, and cytoplasmic and nuclear calcium dynamics, which differentially activate specific transcription factors. Increasing evidence also implicates activity-dependent regulation of epigenetic mechanisms to alter chromatin architecture. Changes in three-dimensional chromatin structure, including chromatin compaction, looping, double-stranded DNA breaks, histone and DNA modification, are altered by action potential activity to selectively inhibit or promote transcription of specific genes. These mechanisms of activity-dependent regulation of gene expression are important in neural development, plasticity, and in neurological and psychological disorders.


2020 ◽  
Vol 21 (18) ◽  
pp. 6816
Author(s):  
Alberto J. López ◽  
Julia K. Hecking ◽  
André O. White

Long-term memory formation requires coordinated regulation of gene expression and persistent changes in cell function. For decades, research has implicated histone modifications in regulating chromatin compaction necessary for experience-dependent changes to gene expression and cell function during memory formation. Recent evidence suggests that another epigenetic mechanism, ATP-dependent chromatin remodeling, works in concert with the histone-modifying enzymes to produce large-scale changes to chromatin structure. This review examines how histone-modifying enzymes and chromatin remodelers restructure chromatin to facilitate memory formation. We highlight the emerging evidence implicating ATP-dependent chromatin remodeling as an essential mechanism that mediates activity-dependent gene expression, plasticity, and cell function in developing and adult brains. Finally, we discuss how studies that target chromatin remodelers have expanded our understanding of the role that these complexes play in substance use disorders.


Genes ◽  
2020 ◽  
Vol 11 (6) ◽  
pp. 641 ◽  
Author(s):  
R. Nicholas Laribee ◽  
Ronit Weisman

The target of rapamycin (TOR) protein kinase is at the core of growth factor- and nutrient-dependent signaling pathways that are well-known for their regulation of metabolism, growth, and proliferation. However, TOR is also involved in the regulation of gene expression, genomic and epigenomic stability. TOR affects nuclear functions indirectly through its activity in the cytoplasm, but also directly through active nuclear TOR pools. The mechanisms by which TOR regulates its nuclear functions are less well-understood compared with its cytoplasmic activities. TOR is an important pharmacological target for several diseases, including cancer, metabolic and neurological disorders. Thus, studies of the nuclear functions of TOR are important for our understanding of basic biological processes, as well as for clinical implications.


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