scholarly journals Dynamics of H3K4me3 Chromatin Marks Take the Lead over H3K27me3 for Gene Regulation during Flower Morphogenesis in Arabidopsis thaliana

2017 ◽  
Author(s):  
Julia Engelhorn ◽  
Robert Blanvillain ◽  
Christian Kröner ◽  
Hugues Parrinello ◽  
Marine Rohmer ◽  
...  
Keyword(s):  
Target Genes ◽  
Gene Activation ◽  
Polycomb Group ◽  
Specific Expression ◽  
Tissue Specific ◽  
Trithorax Group ◽  
Flower Morphogenesis ◽  
Histone 3 ◽  
Genome Wide ◽  
Transcriptional Changes

Plant life-long organogenesis involves sequential, time and tissue specific expression of developmental genes. This requires activities of Polycomb Group (PcG) and trithorax Group complexes, respectively responsible for repressive Histone 3 trimethylation at lysine 27 (H3K27me3) and activation-related H3K4me3. However, the genome-wide dynamics in histone modifications that occur during developmental processes have remained elusive. Here, we report the distributions of H3K27me3 and H3K4me3 along with transcriptional changes, in a developmental series including Arabidopsis leaf and three stages of flower development. We found that chromatin mark levels are highly dynamic over the time series on nearly half of all Arabidopsis genes. Moreover, during early flower morphogenesis, changes in H3K4me3 prime over changes in H3K27me3 and quantitatively correlate with transcription changes, while H3K27me3 changes occur after prolonged expression changes. Notably, early activation of PcG target genes is dominated by increases in H3K4me3 while H3K27me3 remains present at the locus. Our results reveal H3K4me3 as greater predictor over H3K27me3 for transcription dynamics, unveil unexpected chromatin mechanisms at gene activation and underline the relevance of tissue-specific temporal epigenomics.

scholarly journals Kinome-wide RNAi screen uncovers role of Ballchen in maintenance of gene activation by trithorax group in Drosophila

2020 ◽  
Author(s):  
Muhammad Haider Farooq Khan ◽  
Jawad Akhtar ◽  
Zain Umer ◽  
Najma Shaheen ◽  
Ammad Shaukat ◽  
...  
Keyword(s):  
Gene Silencing ◽  
Cell Fate ◽  
Target Genes ◽  
Genetic Interaction ◽  
Ex Vivo ◽  
Gene Activation ◽  
Rnai Screen ◽  
Polycomb Group ◽  
Trithorax Group ◽  
Repressive Effect

AbstractPolycomb group (PcG) and trithorax group (trxG) proteins are evolutionary conserved factors that contribute to cell fate determination and maintenance of cellular identities during development of multicellular organisms. The PcG behaves as repressors to maintain heritable patterns of gene silencing and trxG act as anti-silencing factors by maintaining activation of cell type specific genes. Genetic and molecular analysis has revealed extensive details about how different PcG and trxG complexes antagonize each other to maintain cell fates, however the cellular signaling components that contribute to maintenance of gene expression by PcG/trxG remain elusive. Here, we report an ex vivo kinome-wide RNAi screen in Drosophila aimed to identify cell signaling genes that facilitate trxG to counteract PcG mediated repression. From the list of trxG candidates, Ballchen (BALL), a histone kinase, known to phosphorylate histone H2A at threonine 119 (H2AT119p), was characterized as a trxG regulator. The ball mutant exhibit strong genetic interaction with Polycomb (Pc) and trithorax (trx) mutants and loss of BALL also affects expressions of trxG target genes in ball mutant embryos. BALL co-localizes with Trithorax on chromatin and depletion of BALL results in increased H2AK118 ubiquitination, a histone mark central to PcG mediated gene silencing. Moreover, analysis of genome-wide binding profile of BALL shows an overlap with 85% known binding sites of TRX across the genome. Both BALL and TRX are highly enriched at actively transcribed genes, which also correlate with presence of H3K4me3 and H3K27ac. We propose that BALL mediated signal positively contributes to the maintenance of gene activation by trxG by counteracting the repressive effect of PcG.

scholarly journals Genome-wide RNAi screen in Drosophila reveals Enok as a novel trithorax group regulator

2019 ◽  
Vol 12 (1) ◽  
Author(s):  
Zain Umer ◽  
Jawad Akhtar ◽  
Muhammad Haider Farooq Khan ◽  
Najma Shaheen ◽  
Muhammad Abdul Haseeb ◽  
...  
Keyword(s):  
Hox Genes ◽  
Ex Vivo ◽  
Expression Patterns ◽  
Gene Activation ◽  
Rnai Screen ◽  
Polycomb Group ◽  
Reporter System ◽  
Trithorax Group ◽  
Genome Wide ◽  
A Genome

Abstract Background Polycomb group (PcG) and trithorax group (trxG) proteins contribute to the specialization of cell types by maintaining differential gene expression patterns. Initially discovered as positive regulators of HOX genes in forward genetic screens, trxG counteracts PcG-mediated repression of cell type-specific genes. Despite decades of extensive analysis, molecular understanding of trxG action and regulation are still punctuated by many unknowns. This study aimed at discovering novel factors that elicit an anti-silencing effect to facilitate trxG-mediated gene activation. Results We have developed a cell-based reporter system and performed a genome-wide RNAi screen to discover novel factors involved in trxG-mediated gene regulation in Drosophila. We identified more than 200 genes affecting the reporter in a manner similar to trxG genes. From the list of top candidates, we have characterized Enoki mushroom (Enok), a known histone acetyltransferase, as an important regulator of trxG in Drosophila. Mutants of enok strongly suppressed extra sex comb phenotype of Pc mutants and enhanced homeotic transformations associated with trx mutations. Enok colocalizes with both TRX and PC at chromatin. Moreover, depletion of Enok specifically resulted in an increased enrichment of PC and consequently silencing of trxG targets. This downregulation of trxG targets was also accompanied by a decreased occupancy of RNA-Pol-II in the gene body, correlating with an increased stalling at the transcription start sites of these genes. We propose that Enok facilitates trxG-mediated maintenance of gene activation by specifically counteracting PcG-mediated repression. Conclusion Our ex vivo approach led to identification of new trxG candidate genes that warrant further investigation. Presence of chromatin modifiers as well as known members of trxG and their interactors in the genome-wide RNAi screen validated our reverse genetics approach. Genetic and molecular characterization of Enok revealed a hitherto unknown interplay between Enok and PcG/trxG system. We conclude that histone acetylation by Enok positively impacts the maintenance of trxG-regulated gene activation by inhibiting PRC1-mediated transcriptional repression.

scholarly journals Kinome-Wide RNAi Screen Uncovers Role of Ballchen in Maintenance of Gene Activation by Trithorax Group in Drosophila

2021 ◽  
Vol 9 ◽  
Author(s):  
Muhammad Haider Farooq Khan ◽  
Jawad Akhtar ◽  
Zain Umer ◽  
Najma Shaheen ◽  
Ammad Shaukat ◽  
...  
Keyword(s):  
Gene Silencing ◽  
Cell Fate ◽  
Target Genes ◽  
Ex Vivo ◽  
Gene Activation ◽  
Wide Distribution ◽  
Rnai Screen ◽  
Polycomb Group ◽  
Trithorax Group ◽  
Repressive Effect

Polycomb group (PcG) and trithorax group (trxG) proteins are evolutionary conserved factors that contribute to cell fate determination and maintenance of cellular identities during development of multicellular organisms. The PcG maintains heritable patterns of gene silencing while trxG acts as anti-silencing factors by conserving activation of cell type specific genes. Genetic and molecular analysis has revealed extensive details about how different PcG and trxG complexes antagonize each other to maintain cell fates, however, the cellular signaling components that contribute to the preservation of gene expression by PcG/trxG remain elusive. Here, we report an ex vivo kinome-wide RNAi screen in Drosophila aimed at identifying cell signaling genes that facilitate trxG in counteracting PcG mediated repression. From the list of trxG candidates, Ballchen (BALL), a histone kinase known to phosphorylate histone H2A at threonine 119 (H2AT119p), was characterized as a trxG regulator. The ball mutant exhibits strong genetic interactions with Polycomb (Pc) and trithorax (trx) mutants and loss of BALL affects expression of trxG target genes. BALL co-localizes with Trithorax on chromatin and depletion of BALL results in increased H2AK118 ubiquitination, a histone mark central to PcG mediated gene silencing. Moreover, BALL was found to substantially associate with known TRX binding sites across the genome. Genome wide distribution of BALL also overlaps with H3K4me3 and H3K27ac at actively transcribed genes. We propose that BALL mediated signaling positively contributes to the maintenance of gene activation by trxG in counteracting the repressive effect of PcG.

white+ Transgene Insertions Presenting a Dorsal/Ventral Pattern Define a Single Cluster of Homeobox Genes That Is Silenced by the Polycomb-group Proteins in Drosophila melanogaster

Genetics ◽  
1998 ◽  
Vol 149 (1) ◽  
pp. 257-275 ◽  
Author(s):  
Sophie Netter ◽  
Marie-Odile Fauvarque ◽  
Ruth Diez del Corral ◽  
Jean-Maurice Dura ◽  
Dario Coen
Keyword(s):  
Chromatin Structure ◽  
Target Genes ◽  
Position Effect ◽  
Phenotypic Expression ◽  
Positional Information ◽  
Genomic Region ◽  
Polycomb Group ◽  
Position Effect Variegation ◽  
Trithorax Group ◽  
Clear Cut

AbstractWe used the white gene as an enhancer trap and reporter of chromatin structure. We collected white+ transgene insertions presenting a peculiar pigmentation pattern in the eye: white expression is restricted to the dorsal half of the eye, with a clear-cut dorsal/ventral (D/V) border. This D/V pattern is stable and heritable, indicating that phenotypic expression of the white reporter reflects positional information in the developing eye. Localization of these transgenes led us to identify a unique genomic region encompassing 140 kb in 69D1–3 subject to this D/V effect. This region contains at least three closely related homeobox-containing genes that are constituents of the iroquois complex (IRO-C). IRO-C genes are coordinately regulated and implicated in similar developmental processes. Expression of these genes in the eye is regulated by the products of the Polycomb -group (Pc-G) and trithorax-group (trx-G) genes but is not modified by classical modifiers of position-effect variegation. Our results, together with the report of a Pc -G binding site in 69D, suggest that we have identified a novel cluster of target genes for the Pc-G and trx-G products. We thus propose that ventral silencing of the whole IRO-C in the eye occurs at the level of chromatin structure in a manner similar to that of the homeotic gene complexes, perhaps by local compaction of the region into a heterochromatin-like structure involving the Pc-G products.

scholarly journals Analysis of the Human Tissue-specific Expression by Genome-wide Integration of Transcriptomics and Antibody-based Proteomics

2013 ◽  
Vol 13 (2) ◽  
pp. 397-406 ◽  
Author(s):  
Linn Fagerberg ◽  
Björn M. Hallström ◽  
Per Oksvold ◽  
Caroline Kampf ◽  
Dijana Djureinovic ◽  
...  
Keyword(s):  
Human Tissue ◽  
Specific Expression ◽  
Tissue Specific ◽  
Tissue Specific Expression ◽  
Genome Wide

scholarly journals Tissue-Specific Autoregulation of thestat3 Gene and Its Role in Interleukin-6-Induced Survival Signals in T Cells

2001 ◽  
Vol 21 (19) ◽  
pp. 6615-6625 ◽  
Author(s):  
Masahiro Narimatsu ◽  
Hisoka Maeda ◽  
Shousaku Itoh ◽  
Toru Atsumi ◽  
Takuya Ohtani ◽  
...  
Keyword(s):  
T Cells ◽  
T Lymphocytes ◽  
Interleukin 6 ◽  
Target Genes ◽  
Gene Activation ◽  
Tissue Specific ◽  
Direct Target ◽  
Responsive Element ◽  
Transcription 3

ABSTRACT Signal transducer and activator of transcription 3 (STAT3) mediates signals of various growth factors and cytokines, including interleukin-6 (IL-6). In certain IL-6-responsive cell lines, thestat3 gene is autoregulated by STAT3 through a composite IL-6 response element in its promoter that contains a STAT3-binding element (SBE) and a cyclic AMP-responsive element. To reveal the nature and roles of the stat3 autoregulation in vivo, we generated mice that harbor a mutation in the SBE (stat3 mSBE ). The intact SBE was crucial for IL-6-induced stat3 gene activation in the spleen, especially in the red pulp region, the kidney, and both mature and immature T lymphocytes. The SBE was not required, however, for IL-6-induced stat3 gene activation in hepatocytes. T lymphocytes from the stat3 mSBE/mSBE mice were more susceptible to apoptosis despite the presence of IL-6 than those from wild-type mice. Consistent with this, IL-6-dependent activation of the Pim-1 and junB genes, direct target genes for STAT3, was attenuated in T lymphocytes of thestat3 mSBE/mSBE mice. Thus, the tissue-specific autoregulation of the stat3 gene operates in vivo and plays a role in IL-6-induced antiapoptotic signaling in T cells.

Cinnamon intake reduces serum T3 level and modulates tissue-specific expression of thyroid hormone receptor and target genes in rats

2015 ◽  
Vol 96 (8) ◽  
pp. 2889-2895 ◽  
Author(s):  
Thaiane G Gaique ◽  
Bruna P Lopes ◽  
Luana L Souza ◽  
Gabriela S M Paula ◽  
Carmen C Pazos-Moura ◽  
...  
Keyword(s):  
Thyroid Hormone ◽  
Hormone Receptor ◽  
Target Genes ◽  
Thyroid Hormone Receptor ◽  
Specific Expression ◽  
Tissue Specific ◽  
Tissue Specific Expression ◽  
Serum T3

scholarly journals Cell-specific expression buffering promotes cell survival and cancer robustness

2021 ◽  
Author(s):  
Hao-Kuen Lin ◽  
Jen-Hao Cheng ◽  
Chia-Chou Wu ◽  
Feng-Shu Hsieh ◽  
Carolyn A Dunlap ◽  
...  
Keyword(s):  
Cell Survival ◽  
Rna Seq ◽  
Specific Expression ◽  
Tissue Specific ◽  
Gene Pairs ◽  
Genome Wide ◽  
A Cell ◽  
Physiological Homeostasis ◽  
Multicellular Organisms ◽  
Score Index

Functional buffering ensures biological robustness critical for cell survival and physiological homeostasis in response to environmental challenges. However, in multicellular organisms, the mechanism underlying cell- and tissue-specific buffering and its implications for cancer development remain elusive. Here, we propose a Cell-specific Expression-BUffering (CEBU) mechanism, whereby a gene's function is buffered by cell-specific expression of a buffering gene, to describe functional buffering in humans. The likelihood of CEBU between gene pairs is quantified using a C-score index. By computing C-scores using genome-wide CRISPR screens and transcriptomic RNA-seq of 684 human cell lines, we report that C-score-identified putative buffering gene pairs are enriched for members of the same pathway, protein complex and duplicated gene family. Furthermore, these buffering gene pairs contribute to cell-specific genetic interactions and are indicative of tissue-specific robustness. C-score derived buffering capacities can help predict patient survival in multiple cancers. Our results reveal CEBU as a critical mechanism of functional buffering contributing to cell survival and cancer robustness in humans.

scholarly journals Machine learning identifies six genetic variants and alterations in the Heart Atrial Appendage as key contributors to PD risk predictivity.

2021 ◽  
Author(s):  
Daniel Ho ◽  
William Schierding ◽  
Sophie L Farrow ◽  
Antony Cooper ◽  
Justin M. O'Sullivan ◽  
...  
Keyword(s):  
Machine Learning ◽  
Genetic Variants ◽  
Disease Risk ◽  
Meta Analysis ◽  
Atrial Appendage ◽  
Specific Expression ◽  
Tissue Specific ◽  
Transcriptional Changes ◽  
The Uk ◽  
Eqtl Data

Parkinson disease (PD) is a complex neurodegenerative disease with a range of causes and clinical presentations. Over 76 genetic loci (comprising 90 SNPs) have been associated with PD by the most recent GWAS meta-analysis. Most of these PD-associated variants are located in non-coding regions of the genome and it is difficult to understand what they are doing and how they contribute to the aetiology of PD. We hypothesised that PD-associated genetic variants modulate disease risk through tissue-specific expression quantitative trait loci (eQTL) effects. We developed and validated a machine learning approach that integrated tissue-specific eQTL data on known PD-associated genetic variants with PD case and control genotypes from the Wellcome Trust Case Control Consortium, the UK Biobank, and NeuroX. In so doing, our analysis ranked the tissue-specific transcription effects for PD-associated genetic variants and estimated their relative contributions to PD risk. We identified roles for SNPs that are connected with INPP5P, CNTN1, GBA and SNCA in PD. Ranking the variants and tissue-specific eQTL effects contributing most to the machine learning model suggested a key role in the risk of developing PD for two variants (rs7617877 and rs6808178) and eQTL associated transcriptional changes of EAF1-AS1 within the heart atrial appendage. Similarly, effects associated with eQTLs located within the brain cerebellum were also recognized to confer major PD risk. These findings warrant further mechanistic investigations to determine if these transcriptional changes could act as early contributors to PD risk and disease development.

scholarly journals Interplay between BALL and CBP maintains H3K27 acetylation on active genes in Drosophila

2021 ◽  
Author(s):  
Muhammad Haider Farooq Khan ◽  
Ammad Shaukat ◽  
Zain Umer ◽  
Hina Ahmad ◽  
Muhammad Tariq
Keyword(s):  
Histone Acetyltransferase ◽  
Gene Activation ◽  
Direct Interaction ◽  
Creb Binding Protein ◽  
Drastic Reduction ◽  
Trithorax Group ◽  
Genome Wide ◽  
Histone Kinase ◽  
Trithorax Group Proteins ◽  
Active Genes

CREB binding protein (CBP) is a multifunctional transcriptional co-activator that interacts with a variety of transcription factors and acts as a histone acetyltransferase. In Drosophila, CBP mediated acetylation of histone H3 lysine 27 (H3K27ac) is a known hallmark of gene activation regulated by trithorax group proteins (trxG). Recently, we have shown that a histone kinase Ballchen (BALL) substantially co-localizes with H3K27ac at trxG target loci and is required to maintain gene activation in Drosophila. Here, we report direct interaction between BALL and CBP, which positively regulates H3K27ac. Analysis of genome-wide binding profile of BALL and CBP reveals major overlap and their co-localization at actively transcribed genes. We show that BALL biochemically interacts with CBP and depletion of BALL results in drastic reduction in H3K27ac. Together, these results demonstrate a previously unknown synergy between BALL and CBP and reveals a potentially new pathway required to maintain gene activation during development.

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