scholarly journals The diverse and unanticipated roles of histone deacetylase 9 in coordinating plant development and environmental acclimation

2020 ◽  
Vol 71 (20) ◽  
pp. 6211-6225
Author(s):  
Peter G H de Rooij ◽  
Giorgio Perrella ◽  
Eirini Kaiserli ◽  
Martijn van Zanten
Keyword(s):  
Histone Deacetylase ◽  
Plant Development ◽  
Transcriptional Activation ◽  
Plant Traits ◽  
Feedback Regulation ◽  
Molecular Networks ◽  
Environmental Biology ◽  
Negative Feedback Regulation ◽  
Lysine Residues ◽  
Histone Deacetylase 9

Abstract Plants tightly control gene transcription to adapt to environmental conditions and steer growth and development. Different types of epigenetic modifications are instrumental in these processes. In recent years, an important role for the chromatin-modifying RPD3/HDA1 class I HDAC HISTONE DEACETYLASE 9 (HDA9) emerged in the regulation of a multitude of plant traits and responses. HDACs are widely considered transcriptional repressors and are typically part of multiprotein complexes containing co-repressors, DNA, and histone-binding proteins. By catalyzing the removal of acetyl groups from lysine residues of histone protein tails, HDA9 negatively controls gene expression in many cases, in concert with interacting proteins such as POWERDRESS (PWR), HIGH EXPRESSION OF OSMOTICALLY RESPONSIVE GENES 15 (HOS15), WRKY53, ELONGATED HYPOCOTYL 5 (HY5), ABA INSENSITIVE 4 (ABI4), and EARLY FLOWERING 3 (ELF3). However, HDA9 activity has also been directly linked to transcriptional activation. In addition, following the recent breakthrough discovery of mutual negative feedback regulation between HDA9 and its interacting WRKY-domain transcription factor WRKY53, swift progress in gaining understanding of the biology of HDA9 is expected. In this review, we summarize knowledge on this intriguing versatile—and long under-rated—protein and propose novel leads to further unravel HDA9-governed molecular networks underlying plant development and environmental biology.

scholarly journals SCAP/SREBPs are Central Players in Lipid Metabolism and Novel Metabolic Targets in Cancer Therapy

2018 ◽  
Vol 18 (6) ◽  
pp. 484-493 ◽  
Author(s):  
Xiang Cheng ◽  
Jianying Li ◽  
Deliang Guo
Keyword(s):  
Lipid Metabolism ◽  
Cancer Therapy ◽  
Transcriptional Activation ◽  
Molecular Mechanisms ◽  
Regulatory Element ◽  
Lipid Synthesis ◽  
Feedback Regulation ◽  
Negative Feedback Regulation ◽  
Expression Of Genes ◽  
New Findings

Lipid metabolism reprogramming emerges as a new hallmark of malignancies. Sterol regulatory element-binding proteins (SREBPs), which are central players in lipid metabolism, are endoplasmic reticulum (ER)-bound transcription factors that control the expression of genes important for lipid synthesis and uptake. Their transcriptional activation requires binding to SREBP cleavageactivating protein (SCAP) to translocate their inactive precursors from the ER to the Golgi to undergo cleavage and subsequent nucleus translocation of their NH2-terminal forms. Recent studies have revealed that SREBPs are markedly upregulated in human cancers, providing the mechanistic link between lipid metabolism alterations and malignancies. Pharmacological or genetic inhibition of SCAP or SREBPs significantly suppresses tumor growth in various cancer models, demonstrating that SCAP/SREBPs could serve as promising metabolic targets for cancer therapy. In this review, we will summarize recent progress in our understanding of the underlying molecular mechanisms regulating SCAP/SREBPs and lipid metabolism in malignancies, discuss new findings about SREBP trafficking, which requires SCAP N-glycosylation, and introduce a newly identified microRNA-29-mediated negative feedback regulation of the SCAP/SREBP pathway. Moreover, we will review recently developed inhibitors targeting the SCAP/SREBP pathway for cancer treatment.

scholarly journals β-catenin/LEF-1 Transcription Complex is Responsible for the Transcriptional Activation of LINC01278

2020 ◽  
Author(s):  
Shaojian Lin ◽  
Weiwei Zhang ◽  
Ziwen Shi ◽  
Langping Tan ◽  
Yue Zhu ◽  
...  
Keyword(s):  
Western Blot ◽  
Signaling Pathway ◽  
Transcriptional Activation ◽  
Feedback Regulation ◽  
Luciferase Reporter ◽  
Regulation Mechanism ◽  
Putative Promoter ◽  
Negative Feedback Regulation ◽  
Pathway Activation ◽  
Rna Immunoprecipitation

Abstract Background: Our previous study shows that LINC01278 inhibits the development of papillary thyroid carcinoma (PTC) by regulating miR-376c-3p/DNM3 axis. However, the regulation mechanism of LINC01278 expression in PTC cells is still unclear. Methods: The luciferase reporter and ChIP assays were used to confirme the binding of LEF-1 to the putative promoter site of LINC01278. The RNA immunoprecipitation was used the enrichment of LINC01278 in β-catenin protein. Western blot was used to detected the expression of target proteins. Results: Firstly, the online PROMO algorithm determined a putative LEF-1 binding site on LINC01278 promoter. Then, the luciferase reporter and ChIP assays confirmed the binding of LEF-1 to the putative promoter site of LINC01278. Furthermore, the overexpression of β-catenin increased the binding of LEF-1 to the LINC01278 promoter, and the knockdown or overexpression of LEF-1 or β-catenin can affect the expression level of LINC01278. In addition, RNA immunoprecipitation showed that LINC01278 was enriched in β-catenin protein. RNA pulldown and western blot also confirmed that LINC01278 precipitated β-catenin in TPC-1 and BCPAP cells. Furthermore, the knockdown or overexpression of LINC01278 significantly affected the expression of β-catenin and targets of Wnt/β-catenin signaling pathway (CCND2, CyclinD1, MYC, and SOX4). Conclusion: In summary, we found the transcriptional activation of LINC01278 by the β-catenin/LEF-1 transcription factor, and the negative feedback regulation of LINC01278 on Wnt/β-catenin signaling pathway activation.

scholarly journals HISTONE DEACETYLASE 9 stimulates auxin-dependent thermomorphogenesis in Arabidopsis thaliana by mediating H2A.Z depletion

2019 ◽  
Vol 116 (50) ◽  
pp. 25343-25354 ◽  
Author(s):  
Lennard C. van der Woude ◽  
Giorgio Perrella ◽  
Basten L. Snoek ◽  
Mark van Hoogdalem ◽  
Ondřej Novák ◽  
...  
Keyword(s):  
Arabidopsis Thaliana ◽  
High Temperature ◽  
Histone Deacetylase ◽  
Transcriptional Activation ◽  
Histone Deacetylation ◽  
Shade Avoidance ◽  
Ambient Temperatures ◽  
Histone Deacetylase 9 ◽  
Rate Limiting ◽  
Auxin Accumulation

Many plant species respond to unfavorable high ambient temperatures by adjusting their vegetative body plan to facilitate cooling. This process is known as thermomorphogenesis and is induced by the phytohormone auxin. Here, we demonstrate that the chromatin-modifying enzyme HISTONE DEACETYLASE 9 (HDA9) mediates thermomorphogenesis but does not interfere with hypocotyl elongation during shade avoidance. HDA9 is stabilized in response to high temperature and mediates histone deacetylation at the YUCCA8 locus, a rate-limiting enzyme in auxin biosynthesis, at warm temperatures. We show that HDA9 permits net eviction of the H2A.Z histone variant from nucleosomes associated with YUCCA8, allowing binding and transcriptional activation by PHYTOCHROME INTERACTING FACTOR 4, followed by auxin accumulation and thermomorphogenesis.

scholarly journals Post-transcriptional negative feedback regulation of proteostasis through the Dis3 ribonuclease and its disruption by polyQ-expanded Huntingtin

2019 ◽  
Vol 47 (19) ◽  
pp. 10040-10058
Author(s):  
Ka-Yiu Edwin Kong ◽  
Ting-Ngai Felix Hung ◽  
Pui-Hei Marcus Man ◽  
Tin-Ning Wong ◽  
Tao Cheng ◽  
...  
Keyword(s):  
Heat Stress ◽  
Stress Response ◽  
Negative Feedback ◽  
Transcriptional Activation ◽  
Protein Quality ◽  
Feedback Regulation ◽  
Rna Degradation ◽  
Negative Feedback Regulation ◽  
Heat Stress Response ◽  
Mrna Stabilization

Abstract When proteostasis is disrupted by stresses such as heat shock, the heat stress response will be stimulated, leading to up-regulation of molecular chaperones by transcriptional activation and mRNA stabilization for restoring proteostasis. Although the mechanisms for their transcriptional activation have been clearly defined, how chaperone mRNAs are stabilized remains largely unknown. Starting by exploring the coupling between the apparently unrelated RNA degradation and protein quality control (PQC) systems, we show that the Dis3 ribonuclease, catalytic subunit of the RNA exosome required for RNA degradation, suppresses PQC activity in unstressed cells by degrading mRNAs encoding the Hsp70 cofactors Sis1, Ydj1 and Fes1, as well as some other chaperones or PQC factors, thereby limiting their protein expression. Dis3 is stabilized through its binding to Sis1 and the Hsp70s Ssa1/2. Upon heat stress, loss of Sis1 and Ssa1/2 availability triggers Dis3 ubiquitination and degradation, leading to stabilization of those chaperone mRNAs originally targeted by Dis3. We further demonstrate that polyQ-expanded huntingtin delays Dis3 degradation during heat stress and thus hinders chaperone mRNA stabilization. Our findings not only reveal a post-transcriptional negative feedback loop for maintaining proteostasis, but also uncover a mechanism that contributes to the impaired heat stress response in Huntington's disease.

scholarly journals β-Catenin/LEF-1 transcription complex is responsible for the transcriptional activation of LINC01278

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Shaojian Lin ◽  
Weiwei Zhang ◽  
Ziwen Shi ◽  
Langping Tan ◽  
Yue Zhu ◽  
...  
Keyword(s):  
Transcriptional Activation ◽  
Target Genes ◽  
Feedback Regulation ◽  
Luciferase Reporter ◽  
Protein Accumulation ◽  
Regulation Mechanism ◽  
Putative Promoter ◽  
Negative Feedback Regulation ◽  
Proteasome Degradation ◽  
Rna Immunoprecipitation

Abstract Background Our previous study shows that LINC01278 inhibits the malignant proliferation and invasion of papillary thyroid carcinoma (PTC) cells by regulating the miR-376c-3p/DNM3 axis. However, the regulation mechanism of LINC01278 expression in PTC cells is still unclear. Methods The luciferase reporter and ChIP assays were used to confirm the binding of LEF-1 to the putative promoter site of LINC01278 gene. The RNA immunoprecipitation and RNA pulldown were used to determine the enrichment of LINC01278 in β-catenin protein. The proteasome inhibitors (MG132) was used for detecting the β-catenin ubiquitination-proteasome degradation. Wnt/β-catenin specific agonists (LiCI), inhibitors (WiKI4) and TOP/FOP-flash reporter assay were used for detecting the activation of Wnt/β-catenin signal. Western blot was used to detected the expression of target proteins. Results The online PROMO algorithm determines a putative LEF-1 binding site on LINC01278 promoter, the LEF-1 binds to the putative promoter site of LINC01278 gene, and β-catenin enhances the binding of LEF-1 to the LINC01278 gene promoter. Furthermore, LINC01278 negatively regulated the protein accumulation of β-catenin in the cytoplasm, into nucleus, and ultimately inhibited the transcription of downstream target genes activated by Wnt/β-catenin signal. The results of RNA immunoprecipitation and RNA pulldown proved the direct binding of LINC01278 to β-catenin protein. In addition, the combination of LINC01278 and β-catenin promotes the β-catenin ubiquitination-proteasome degradation. Conclusion In summary, we found the transcriptional activation of LINC01278 by the β-catenin/LEF-1 transcription factor, and the negative feedback regulation of LINC01278 onβ-catenin signal.

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