Histone Post-Translational Modifications and Nucleosome Organisation in Transcriptional Regulation: Some Open Questions

2017 ◽  
pp. 65-92 ◽  
Author(s):  
Josefa Castillo ◽  
Gerardo López-Rodas ◽  
Luis Franco
Keyword(s):  
Transcriptional Regulation ◽  
Post Translational Modifications ◽  
Open Questions

scholarly journals TFEB Signalling-Related MicroRNAs and Autophagy

Biomolecules ◽  
2021 ◽  
Vol 11 (7) ◽  
pp. 985
Author(s):  
Davide Corà ◽  
Federico Bussolino ◽  
Gabriella Doronzo
Keyword(s):  
Transcriptional Regulation ◽  
Stress Factors ◽  
Cellular Functions ◽  
Post Translational Modifications ◽  
Cellular Processes ◽  
Factor Deficiency ◽  
Transcription Factor Eb ◽  
Important Regulator ◽  
Response To Stress ◽  
Post Transcriptional Regulation

The oncogenic Transcription Factor EB (TFEB), a member of MITF-TFE family, is known to be the most important regulator of the transcription of genes responsible for the control of lysosomal biogenesis and functions, autophagy, and vesicles flux. TFEB activation occurs in response to stress factors such as nutrient and growth factor deficiency, hypoxia, lysosomal stress, and mitochondrial damage. To reach the final functional status, TFEB is regulated in multimodal ways, including transcriptional rate, post-transcriptional regulation, and post-translational modifications. Post-transcriptional regulation is in part mediated by miRNAs. miRNAs have been linked to many cellular processes involved both in physiology and pathology, such as cell migration, proliferation, differentiation, and apoptosis. miRNAs also play a significant role in autophagy, which exerts a crucial role in cell behaviour during stress or survival responses. In particular, several miRNAs directly recognise TFEB transcript or indirectly regulate its function by targeting accessory molecules or enzymes involved in its post-translational modifications. Moreover, the transcriptional programs triggered by TFEB may be influenced by the miRNA-mediated regulation of TFEB targets. Finally, recent important studies indicate that the transcription of many miRNAs is regulated by TFEB itself. In this review, we describe the interplay between miRNAs with TFEB and focus on how these types of crosstalk affect TFEB activation and cellular functions.

The roles of post-translational modifications and coactivators of STAT6 signaling in tumor growth and progression

2020 ◽  
Vol 12 (21) ◽  
pp. 1945-1960
Author(s):  
Hao Huang ◽  
Yizhou Zheng ◽  
Linfu Li ◽  
Weimei Shi ◽  
Rui Zhang ◽  
...  
Keyword(s):  
Transcriptional Regulation ◽  
Tumor Growth ◽  
Poor Prognosis ◽  
Molecular Mechanisms ◽  
Structural Characteristics ◽  
Tumor Development ◽  
Metastatic Tumors ◽  
Post Translational Modifications ◽  
Signal Transducers ◽  
Development And Management

Signal transducers and activators of transcription 6 (STAT6) are highly expressed in various tumors and associated with tumorigenesis, immunosuppression, proliferation, metastasis and poor prognosis in human cancers. In response to IL-4/13, STAT6 is phosphorylated, dimerizes and triggers transcriptional regulation after recruitment of coactivators to transcriptosome, such as CBP/p300, SRC-1, PARP-14 and PSF. Post-translational modifications, including phosphorylation, ubiquitination, ADP-ribosylation and acetylation, have been explored for molecular mechanisms of STAT6 in tumor development and management. STAT6 has been developed as a specific biomarker for distinguishing and diagnosing tumor phenotypes, although it is observed to be frequently mutated in metastatic tumors. In this article, we focus mainly on the structural characteristics of STAT6 and its role in tumor growth and progression.

scholarly journals Peptidyl Arginine Deiminase 2 (PADI2)-Mediated Arginine Citrullination Modulates Transcription in Cancer

2020 ◽  
Vol 21 (4) ◽  
pp. 1351 ◽  
Author(s):  
Miguel Beato ◽  
Priyanka Sharma
Keyword(s):  
Transcriptional Regulation ◽  
Rna Polymerase Ii ◽  
Cancer Progression ◽  
Neurological Disorders ◽  
Breast Cancer Cells ◽  
Arginine Deiminase ◽  
Post Translational Modifications ◽  
Pathological Conditions ◽  
Epigenetic Events ◽  
Functional Implications

Protein arginine deimination leading to the non-coded amino acid citrulline remains a key question in the field of post-translational modifications ever since its discovery by Rogers and Simmonds in 1958. Citrullination is catalyzed by a family of enzymes called peptidyl arginine deiminases (PADIs). Initially, increased citrullination was associated with autoimmune diseases, including rheumatoid arthritis and multiple sclerosis, as well as other neurological disorders and multiple types of cancer. During the last decade, research efforts have focused on how citrullination contributes to disease pathogenesis by modulating epigenetic events, pluripotency, immunity and transcriptional regulation. However, our knowledge regarding the functional implications of citrullination remains quite limited, so we still do not completely understand its role in physiological and pathological conditions. Here, we review the recently discovered functions of PADI2-mediated citrullination of the C-terminal domain of RNA polymerase II in transcriptional regulation in breast cancer cells and the proposed mechanisms to reshape the transcription regulatory network that promotes cancer progression.

scholarly journals Molecular Processes Connecting DNA Methylation Patterns with DNA Methyltransferases and Histone Modifications in Mammalian Genomes

Genes ◽  
2018 ◽  
Vol 9 (11) ◽  
pp. 566 ◽  
Author(s):  
Albert Jeltsch ◽  
Julian Broche ◽  
Pavel Bashtrykov
Keyword(s):  
Dna Methylation ◽  
Chromatin Modification ◽  
Dna Methyltransferases ◽  
Nucleosome Remodeling ◽  
Post Translational Modifications ◽  
Open Questions ◽  
Mammalian Genomes ◽  
Methylation Patterns ◽  
The Impact ◽  
Human And Mouse

DNA methylation is an essential part of the epigenome chromatin modification network, which also comprises several covalent histone protein post-translational modifications. All these modifications are highly interconnected, because the writers and erasers of one mark, DNA methyltransferases (DNMTs) and ten eleven translocation enzymes (TETs) in the case of DNA methylation, are directly or indirectly targeted and regulated by other marks. Here, we have collected information about the genomic distribution and variability of DNA methylation in human and mouse DNA in different genomic elements. After summarizing the impact of DNA methylation on genome evolution including CpG depletion, we describe the connection of DNA methylation with several important histone post-translational modifications, including methylation of H3K4, H3K9, H3K27, and H3K36, but also with nucleosome remodeling. Moreover, we present the mechanistic features of mammalian DNA methyltransferases and their associated factors that mediate the crosstalk between DNA methylation and chromatin modifications. Finally, we describe recent advances regarding the methylation of non-CpG sites, methylation of adenine residues in human cells and methylation of mitochondrial DNA. At several places, we highlight controversial findings or open questions demanding future experimental work.

scholarly journals Transcriptional regulation of cell shape during organ morphogenesis

2018 ◽  
Vol 217 (9) ◽  
pp. 2987-3005 ◽  
Author(s):  
Aravind Sivakumar ◽  
Natasza A. Kurpios
Keyword(s):  
Transcriptional Regulation ◽  
Cell Shape ◽  
Evolutionary Conservation ◽  
Model Organisms ◽  
Critical Question ◽  
Organ Morphogenesis ◽  
Open Questions ◽  
Cell Shape Changes ◽  
Shape Changes

The emerging field of transcriptional regulation of cell shape changes aims to address the critical question of how gene expression programs produce a change in cell shape. Together with cell growth, division, and death, changes in cell shape are essential for organ morphogenesis. Whereas most studies of cell shape focus on posttranslational events involved in protein organization and distribution, cell shape changes can be genetically programmed. This review highlights the essential role of transcriptional regulation of cell shape during morphogenesis of the heart, lungs, gastrointestinal tract, and kidneys. We emphasize the evolutionary conservation of these processes across different model organisms and discuss perspectives on open questions and research avenues that may provide mechanistic insights toward understanding birth defects.

scholarly journals Genomic locus proteomic screening identifies the NF-κB signaling pathway components NFκB1 and IKBKG as transcriptional regulators of Ripk3 in endothelial cells

PLoS ONE ◽  
2021 ◽  
Vol 16 (6) ◽  
pp. e0253519
Author(s):  
Siqi Gao ◽  
Matthew Menendez ◽  
Katarzyna Kurylowicz ◽  
Courtney T. Griffin
Keyword(s):  
Endothelial Cells ◽  
Transcriptional Regulation ◽  
Signaling Pathway ◽  
Functional Protein ◽  
Genomic Locus ◽  
Interacting Protein ◽  
Vascular Integrity ◽  
Post Translational Modifications ◽  
Coregulatory Proteins ◽  
Light Chain Enhancer

The receptor-interacting protein kinase 3 (RIPK3) is a multi-functional protein best known for facilitating cellular necroptosis and inflammation. Recent evidence from our lab indicates that RIPK3 expression must be tightly regulated in endothelial cells to promote angiogenesis, to maintain vascular integrity during embryogenesis, and to provide protection from postnatal atherosclerosis. RIPK3 activity and stability are regulated by post-translational modifications and caspase-dependent cleavage. However, less is known about the transcriptional regulation of Ripk3. Here we utilized an unbiased CRISPR-based technology called genomic locus proteomics (GLoPro) to screen transcription factors and coregulatory proteins associated with the Ripk3 locus in a murine endothelial cell line. We found that 41 nuclear proteins are specifically enriched at the Ripk3 locus, including the Nuclear Factor kappa-light-chain-enhancer of activated B cells (NF-κB) signaling pathway components NFκB1 and IKBKG. We further verified that NFκB1 and IKBKG directly bind the Ripk3 promoter and prevent TNFα-induced Ripk3 transcription in cultured human primary endothelial cells. Moreover, NFκB1 prevents RIPK3-mediated death of primary endothelial cells. These data provide new insights into NF-κB signaling and Ripk3 transcriptional regulation in endothelial cells.

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