scholarly journals Chiffon triggers global histone H3 acetylation and expression of developmental genes in Drosophila embryos

2021 ◽  
Author(s):  
Eliana F. Torres-Zelada ◽  
Smitha George ◽  
Hannah R. Blum ◽  
Vikki M. Weake
Keyword(s):  
Gene Expression ◽  
Histone Acetylation ◽  
Potential Role ◽  
Developmental Genes ◽  
Histone Acetyltransferase Gcn5 ◽  
Genome Activation ◽  
H3 Acetylation ◽  
Drosophila Embryos ◽  
Cell Cycle Kinase ◽  
Zygotic Genome

The histone acetyltransferase Gcn5 is critical for gene expression and development. In Drosophila, Gcn5 is part of four complexes (SAGA, ATAC, CHAT, and ADA) that are essential for fly viability and have key roles in regulating gene expression. Here, we show that while the SAGA, ADA, and CHAT complexes play redundant roles in embryonic gene expression, the insect-specific CHAT complex uniquely regulates expression of a subset of developmental genes. We also identify a substantial decrease in histone acetylation in chiffon mutant embryos that exceeds that observed in ada2b, suggesting broader roles for Chiffon in regulating histone acetylation outside of the Gcn5 complexes. The chiffon gene encodes two independent polypeptides that nucleate formation of either the CHAT or Dbf4-dependent kinase (DDK) complexes. DDK includes the cell cycle kinase Cdc7, which is necessary for maternally-driven DNA replication in the embryo. We identify a temporal switch between the expression of these chiffon gene products during a short window during the early nuclear cycles in embryos that correlates with the onset of zygotic genome activation, suggesting a potential role for CHAT in this process.

scholarly journals Behavioral sensitization induced by methamphetamine causes differential alterations in gene expression and histone acetylation of the prefrontal cortex in rats

2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Hui Li ◽  
Jing-An Chen ◽  
Qian-Zhi Ding ◽  
Guan-Yi Lu ◽  
Ning Wu ◽  
...  
Keyword(s):  
Gene Expression ◽  
Prefrontal Cortex ◽  
Histone Acetylation ◽  
Differentially Expressed Genes ◽  
Behavioral Sensitization ◽  
Functional Enrichment ◽  
Differentially Expressed ◽  
Adult Rats ◽  
Mrna Microarray ◽  
H3 Acetylation

Abstract Background Methamphetamine (METH) is one of the most widely abused illicit substances worldwide; unfortunately, its addiction mechanism remains unclear. Based on accumulating evidence, changes in gene expression and chromatin modifications might be related to the persistent effects of METH on the brain. In the present study, we took advantage of METH-induced behavioral sensitization as an animal model that reflects some aspects of drug addiction and examined the changes in gene expression and histone acetylation in the prefrontal cortex (PFC) of adult rats. Methods We conducted mRNA microarray and chromatin immunoprecipitation (ChIP) coupled to DNA microarray (ChIP-chip) analyses to screen and identify changes in transcript levels and histone acetylation patterns. Functional enrichment analyses, including Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses, were performed to analyze the differentially expressed genes. We then further identified alterations in ANP32A (acidic leucine-rich nuclear phosphoprotein-32A) and POU3F2 (POU domain, class 3, transcription factor 2) using qPCR and ChIP-PCR assays. Results In the rat model of METH-induced behavioral sensitization, METH challenge caused 275 differentially expressed genes and a number of hyperacetylated genes (821 genes with H3 acetylation and 10 genes with H4 acetylation). Based on mRNA microarray and GO and KEGG enrichment analyses, 24 genes may be involved in METH-induced behavioral sensitization, and 7 genes were confirmed using qPCR. We further examined the alterations in the levels of the ANP32A and POU3F2 transcripts and histone acetylation at different periods of METH-induced behavioral sensitization. H4 hyperacetylation contributed to the increased levels of ANP32A mRNA and H3/H4 hyperacetylation contributed to the increased levels of POU3F2 mRNA induced by METH challenge-induced behavioral sensitization, but not by acute METH exposure. Conclusions The present results revealed alterations in transcription and histone acetylation in the rat PFC by METH exposure and provided evidence that modifications of histone acetylation contributed to the alterations in gene expression caused by METH-induced behavioral sensitization.

CLAMP regulates Zygotic Genome Activation in Drosophila embryos

Genetics ◽  
2021 ◽  
Author(s):  
Megan M Colonnetta ◽  
Juan E Abrahante ◽  
Paul Schedl ◽  
Daryl M Gohl ◽  
Girish Deshpande
Keyword(s):  
Temporal Dynamics ◽  
Embryonic Patterning ◽  
Zygotic Genome Activation ◽  
Promoter Sequences ◽  
Genome Wide ◽  
Zygotic Transcription ◽  
Pioneer Factor ◽  
Genome Activation ◽  
Drosophila Embryos ◽  
Zygotic Genome

Abstract Embryonic patterning is critically dependent on zygotic genome activation (ZGA). In Drosophila melanogaster embryos, the pioneer factor Zelda directs ZGA, possibly in conjunction with other factors. Here we have explored novel involvement of Chromatin-Linked Adapter for MSL Proteins (CLAMP) during ZGA. CLAMP binds thousands of sites genome-wide throughout early embryogenesis. Interestingly, CLAMP relocates to target promoter sequences across the genome when ZGA is initiated. Although there is a considerable overlap between CLAMP and Zelda binding sites, the proteins display distinct temporal dynamics. To assess whether CLAMP occupancy affects gene expression, we analyzed transcriptomes of embryos zygotically compromised for either clamp or zelda and found that transcript levels of many zygotically-activated genes are similarly affected. Importantly, compromising either clamp or zelda disrupted the expression of critical segmentation and sex determination genes bound by CLAMP (and Zelda). Furthermore, clamp knockdown embryos recapitulate other phenotypes observed in Zelda-depleted embryos, including nuclear division defects, centrosome aberrations, and a disorganized actomyosin network. Based on these data, we propose that CLAMP acts in concert with Zelda to regulate early zygotic transcription.

scholarly journals Pluripotency factors select gene expression repertoire at Zygotic Genome Activation

2020 ◽  
Author(s):  
Meijiang Gao ◽  
Marina Veil ◽  
Marcus Rosenblatt ◽  
Anna Gebhard ◽  
Helge Hass ◽  
...  
Keyword(s):  
Gene Expression ◽  
Transcription Factors ◽  
Early Gene ◽  
Zebrafish Embryos ◽  
Fate Specification ◽  
Pluripotency Factors ◽  
Zygotic Transcription ◽  
Simultaneous Loss ◽  
Genome Activation ◽  
Zygotic Genome

AbstractAwakening of zygotic transcription in animal embryos relies on maternal pioneer transcription factors. The interplay of global and specific functions of these proteins remains poorly understood. Here, we analyzed nucleosome positioning, H3K27 acetylation, transcription, and gastrulation rates in zebrafish embryos lacking pluripotency factors Pou5f3 and Sox19b. We show that the bulk transcriptional onset does not require Sox19b and Pou5f3, but is sensitive to their balance. Pou5f3 docks H3K27ac on the enhancers of genes involved in gastrulation and ventral fate specification. Sox19b facilitates Pou5f3 access to one-third of these enhancers. The genes regulating mesendodermal and dorsal fates are primed for activation independently on Pou5f3 and Sox19b. Strikingly, the loss of either factor results in activation of silent enhancers; simultaneous loss of both leads to premature expression of differentiation genes. Our results uncover how independent activities of maternal Pou5f3 and Sox19b add up or antagonize to determine the early gene expression repertoire.

scholarly journals Combinatorial action of NF–Y and TALE at embryonic enhancers defines distinct gene expression programs during zygotic genome activation in zebrafish

2020 ◽  
Vol 459 (2) ◽  
pp. 161-180 ◽  
Author(s):  
William Stanney ◽  
Franck Ladam ◽  
Ian J. Donaldson ◽  
Teagan J. Parsons ◽  
René Maehr ◽  
...  
Keyword(s):  
Gene Expression ◽  
Zygotic Genome Activation ◽  
Distinct Gene ◽  
Genome Activation ◽  
Zygotic Genome

scholarly journals Behavioral Sensitization Induced by Methamphetamine Causes Differential Alterations in Gene Expression and Histone Acetylation of the Prefrontal Cortex in Rats

2020 ◽  
Author(s):  
Hui Li ◽  
Jing-An Chen ◽  
Qian-Zhi Ding ◽  
Guan-Yi Lu ◽  
Ning Wu ◽  
...  
Keyword(s):  
Gene Expression ◽  
Prefrontal Cortex ◽  
Histone Acetylation ◽  
Differentially Expressed Genes ◽  
Behavioral Sensitization ◽  
Functional Enrichment ◽  
Differentially Expressed ◽  
Adult Rats ◽  
Mrna Microarray ◽  
H3 Acetylation

Abstract Background: Methamphetamine (METH) is one of the most widely abused illicit substances worldwide; unfortunately, its addiction mechanism remains unclear. Based on accumulating evidence, changes in gene expression and chromatin modifications might be related to the persistent effects of METH on the brain. In the present study, we took advantage of METH-induced behavioral sensitization as an animal model that reflects some aspects of drug addiction and examined the changes in gene expression and histone acetylation in the prefrontal cortex (PFC) of adult rats.Methods: We conducted mRNA microarray and chromatin immunoprecipitation (ChIP) coupled to DNA microarray (ChIP-chip) analyses to screen and identify changes in transcript levels and histone acetylation patterns. Functional enrichment analyses, including Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses, were performed to analyze the differentially expressed genes. We then further identified alterations in ANP32A (acidic leucine-rich nuclear phosphoprotein-32A) and POU3F2 (POU domain, class 3, transcription factor 2) using qPCR and ChIP-PCR assays.Results: In the rat model of METH-induced behavioral sensitization, METH challenge caused 275 differentially expressed genes and a number of hyperacetylated genes (821 genes with H3 acetylation and 10 genes with H4 acetylation). Based on mRNA microarray and GO and KEGG enrichment analyses, 24 genes may be involved in METH-induced behavioral sensitization, and 7 were confirmed using qPCR. We further examined the alterations in the levels of the ANP32A and POU3F2 transcripts and histone acetylation at different periods of METH-induced behavioral sensitization. H4 hyperacetylation contributed to the increased levels of ANP32A mRNA and H3/H4 hyperacetylation contributed to the increased levels of POU3F2 mRNA induced by METH challenge-induced behavioral sensitization, but not by acute METH exposure.Conclusions: The present results revealed alterations in transcription and histone acetylation in the rat PFC by METH exposure and provided evidence that modifications of histone acetylation contributed to the alterations in gene expression caused by METH-induced behavioral sensitization.

scholarly journals The genome-wide multi-layered architecture of chromosome pairing in early Drosophila embryos

2019 ◽  
Vol 10 (1) ◽  
Author(s):  
Jelena Erceg ◽  
Jumana AlHaj Abed ◽  
Anton Goloborodko ◽  
Bryan R. Lajoie ◽  
Geoffrey Fudenberg ◽  
...  
Keyword(s):  
Computational Approach ◽  
Homologous Chromosomes ◽  
Layered Architecture ◽  
Homolog Pairing ◽  
Genome Wide ◽  
Mammalian Embryos ◽  
Pioneer Factor ◽  
Genome Activation ◽  
Drosophila Embryos ◽  
Zygotic Genome

Abstract Genome organization involves cis and trans chromosomal interactions, both implicated in gene regulation, development, and disease. Here, we focus on trans interactions in Drosophila, where homologous chromosomes are paired in somatic cells from embryogenesis through adulthood. We first address long-standing questions regarding the structure of embryonic homolog pairing and, to this end, develop a haplotype-resolved Hi-C approach to minimize homolog misassignment and thus robustly distinguish trans-homolog from cis contacts. This computational approach, which we call Ohm, reveals pairing to be surprisingly structured genome-wide, with trans-homolog domains, compartments, and interaction peaks, many coinciding with analogous cis features. We also find a significant genome-wide correlation between pairing, transcription during zygotic genome activation, and binding of the pioneer factor Zelda. Our findings reveal a complex, highly structured organization underlying homolog pairing, first discovered a century ago in Drosophila. Finally, we demonstrate the versatility of our haplotype-resolved approach by applying it to mammalian embryos.

scholarly journals Prepatterning of Developmental Gene Expression by Modified Histones before Zygotic Genome Activation

2011 ◽  
Vol 21 (6) ◽  
pp. 993-1004 ◽  
Author(s):  
Leif C. Lindeman ◽  
Ingrid S. Andersen ◽  
Andrew H. Reiner ◽  
Nan Li ◽  
Håvard Aanes ◽  
...  
Keyword(s):  
Gene Expression ◽  
Zygotic Genome Activation ◽  
Developmental Gene ◽  
Developmental Gene Expression ◽  
Genome Activation ◽  
Zygotic Genome

scholarly journals Establishment of developmental gene silencing by ordered polycomb complex recruitment in early zebrafish embryos

eLife ◽  
2022 ◽  
Vol 11 ◽  
Author(s):  
Graham JM Hickey ◽  
Candice L Wike ◽  
Xichen Nie ◽  
Yixuan Guo ◽  
Mengyao Tan ◽  
...  
Keyword(s):  
Zebrafish Embryos ◽  
Dna Hypomethylation ◽  
Developmental Gene ◽  
Developmental Genes ◽  
Chromatin States ◽  
Vertebrate Embryos ◽  
Polycomb Repressive Complex 1 ◽  
Genome Activation ◽  
Polycomb Complex ◽  
Zygotic Genome

Vertebrate embryos achieve developmental competency during zygotic genome activation (ZGA) by establishing chromatin states that silence yet poise developmental genes for subsequent lineage-specific activation. Here, we reveal the order of chromatin states in establishing developmental gene poising in preZGA zebrafish embryos. Poising is established at promoters and enhancers that initially contain open/permissive chromatin with 'Placeholder' nucleosomes (bearing H2A.Z, H3K4me1, and H3K27ac), and DNA hypomethylation. Silencing is initiated by the recruitment of Polycomb Repressive Complex 1 (PRC1), and H2Aub1 deposition by catalytic Rnf2 during preZGA and ZGA stages. During postZGA, H2Aub1 enables Aebp2-containing PRC2 recruitment and H3K27me3 deposition. Notably, preventing H2Aub1 (via Rnf2 inhibition) eliminates recruitment of Aebp2-PRC2 and H3K27me3, and elicits transcriptional upregulation of certain developmental genes during ZGA. However, upregulation is independent of H3K27me3 - establishing H2Aub1 as the critical silencing modification at ZGA. Taken together, we reveal the logic and mechanism for establishing poised/silent developmental genes in early vertebrate embryos.

scholarly journals Quantitative imaging of transcription in living Drosophila embryos reveals the impact of core promoter motifs on promoter state dynamics

2021 ◽  
Author(s):  
Virginia L Pimmett ◽  
Matthieu Dejean ◽  
Carola Fernandez ◽  
Antonio Trullo ◽  
Edouard Bertrand ◽  
...  
Keyword(s):  
Core Promoter ◽  
Quantitative Imaging ◽  
Tata Box ◽  
Polymerase Pausing ◽  
Multicellular Organisms ◽  
Genome Activation ◽  
The Impact ◽  
Rate Limiting ◽  
Drosophila Embryos ◽  
Zygotic Genome

AbstractGenes are expressed in stochastic transcriptional bursts linked to alternating active and inactive promoter states. A major challenge in transcription is understanding how promoter composition dictates bursting, particularly in multicellular organisms. We investigate two key Drosophila developmental promoter motifs, the TATA box (TATA) and the Initiator (INR). Using live imaging in Drosophila embryos and new computational methods, we demonstrate that bursting occurs on multiple timescales ranging from seconds to minutes. TATA-containing promoters and INR-containing promoters exhibit distinct dynamics, with one or two separate rate-limiting steps respectively. A TATA box is associated with long active states, high rates of polymerase initiation, and short-lived, infrequent inactive states. In contrast, the INR motif leads to two inactive states, one of which relates to promoter-proximal polymerase pausing. Surprisingly, the model suggests pausing is not obligatory, but occurs stochastically for a subset of polymerases. Overall, our results provide a rationale for promoter switching during zygotic genome activation.

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