Fine tuning of RFX/DAF-19-regulated target gene expression through binding to multiple sites in Caenorhabditis elegans

The glioma-associated oncogene (GLI) family consists of GLI1, GLI2, and GLI3 in mammals. This family has important roles in development and homeostasis. To achieve these roles, the GLI family has widespread outputs. GLI activity is therefore strictly regulated at multiple levels, including via post-translational modifications for context-dependent GLI target gene expression. The protein arginine methyl transferase (PRMT) family is also associated with embryogenesis, homeostasis, and cancer mainly via epigenetic modifications. In the PRMT family, PRMT1, PRMT5, and PRMT7 reportedly regulate GLI1 and GLI2 activity. PRMT1 methylates GLI1 to upregulate its activity and target gene expression. Cytoplasmic PRMT5 methylates GLI1 and promotes GLI1 protein stabilization. Conversely, nucleic PRMT5 interacts with MENIN to suppress growth arrest-specific protein 1 expression, which assists Hedgehog ligand binding to Patched, indirectly resulting in downregulated GLI1 activity. PRMT7-mediated GLI2 methylation upregulates its activity through the dissociation of GLI2 and Suppressor of Fused. Together, PRMT1, PRMT5, and PRMT7 regulate GLI activity at multiple revels. Furthermore, the GLI and PRMT families have strong links with various cancers through cancer stem cell maintenance. Therefore, PRMT-mediated regulation of GLI activity would have important roles in cancer stem cell maintenance.

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Fine-Tuning of GLI Activity Through Arginine Methylation: Its Mechanisms and Function

10.20944/preprints202008.0455.v1 ◽

2020 ◽

Author(s):

Yoshinori Abe ◽

Nobuyuki Tanaka

Keyword(s):

Gene Expression ◽

Hedgehog Signaling ◽

Target Gene ◽

Arginine Methylation ◽

Specific Protein ◽

Protein Stabilization ◽

Fine Tuning ◽

Methyl Transferase ◽

Target Gene Expression ◽

Multiple Levels

The glioma-associated oncogene (GLI) family consists of GLI1, GLI2, and GLI3 in mammals, and is the effector in the Hedgehog signaling pathway. This family has important roles in the development and homeostasis of various tissues. To achieve these roles, the GLI family has widespread outputs. GLI activity is therefore strictly regulated at multiple levels, including via post-translational modifications for context-dependent GLI target gene expression. Conversely, dysregulated GLI activation has strong links with a variety of cancers. The protein arginine methyl transferase (PRMT) family is also associated with embryogenesis, homeostasis, and cancer via epigenetic modifications and signal transduction. In the PRMT family, PRMT1, PRMT5, and PRMT7 reportedly regulate GLI1 and GLI2 activity. PRMT1 methylates GLI1 to upregulate its activity and target gene expression. Cytoplasmic PRMT5 methylates GLI1 and is involved in GLI1 protein stabilization. In contrast, nucleic PRMT5 interacts with MENIN to suppress growth arrest-specific protein 1 expression, which assists Hedgehog ligand binding to Patched, indirectly resulting in downregulated GLI1 activity. PRMT7-mediated GLI2 methylation upregulates its activity through the dissociation of GLI2 and Suppressor of Fused. Therefore, PRMT1, PRMT5, and PRMT7 regulate GLI activity at multiple levels, and PRMT-mediated GLI dysregulation may be involved in cancer formation.

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2049-P: The Chd4 Helicase of the Nucleosome Remodeling and Deacetylase Complex Modulates Pdx1 Target Gene Expression In Vitro

Diabetes ◽

10.2337/db20-2049-p ◽

2020 ◽

Vol 69 (Supplement 1) ◽

pp. 2049-P

Author(s):

REBECCA K. DAVIDSON ◽

NOLAN CASEY ◽

JASON SPAETH

Keyword(s):

Gene Expression ◽

Target Gene ◽

Nucleosome Remodeling ◽

Target Gene Expression

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On the way toward regulatable expression systems in acetic acid bacteria: target gene expression and use cases

Applied Microbiology and Biotechnology ◽

10.1007/s00253-021-11269-z ◽

2021 ◽

Author(s):

Philipp Moritz Fricke ◽

Angelika Klemm ◽

Michael Bott ◽

Tino Polen

Keyword(s):

Gene Expression ◽

Acetic Acid ◽

Literature Search ◽

Target Gene ◽

Target Genes ◽

Recombinant Dna ◽

Acetic Acid Bacteria ◽

Homoserine Lactone ◽

Expression Systems ◽

Target Gene Expression

Abstract Acetic acid bacteria (AAB) are valuable biocatalysts for which there is growing interest in understanding their basics including physiology and biochemistry. This is accompanied by growing demands for metabolic engineering of AAB to take advantage of their properties and to improve their biomanufacturing efficiencies. Controlled expression of target genes is key to fundamental and applied microbiological research. In order to get an overview of expression systems and their applications in AAB, we carried out a comprehensive literature search using the Web of Science Core Collection database. The Acetobacteraceae family currently comprises 49 genera. We found overall 6097 publications related to one or more AAB genera since 1973, when the first successful recombinant DNA experiments in Escherichia coli have been published. The use of plasmids in AAB began in 1985 and till today was reported for only nine out of the 49 AAB genera currently described. We found at least five major expression plasmid lineages and a multitude of further expression plasmids, almost all enabling only constitutive target gene expression. Only recently, two regulatable expression systems became available for AAB, an N-acyl homoserine lactone (AHL)-inducible system for Komagataeibacter rhaeticus and an l-arabinose-inducible system for Gluconobacter oxydans. Thus, after 35 years of constitutive target gene expression in AAB, we now have the first regulatable expression systems for AAB in hand and further regulatable expression systems for AAB can be expected. Key points • Literature search revealed developments and usage of expression systems in AAB. • Only recently 2 regulatable plasmid systems became available for only 2 AAB genera. • Further regulatable expression systems for AAB are in sight.

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