scholarly journals The MLL3/4 complexes and MiDAC act antagonistically as genome-wide regulators of H4K20ac to control a specific gene expression program

2021 ◽  
Author(s):  
Xiaokang Wang ◽  
Wojciech Rosikiewicz ◽  
Yurii Sedkov ◽  
Baisakhi Mondal ◽  
Satish Kallappagoudar ◽  
...  
Keyword(s):  
Gene Expression ◽  
Physiological Role ◽  
Specific Gene ◽  
Physical Interaction ◽  
Specific Gene Expression ◽  
Genome Wide ◽  
Histone H3k27 ◽  
Genomic Regions ◽  
Transcriptional Output ◽  
Expression Program

The mitotic deacetylase complex MiDAC has recently been shown to play a vital physiological role in embryonic development and neurite outgrowth. However, how MiDAC functionally intersects with other chromatin-modifying regulators is poorly understood. Here, we describe a physical interaction between the histone H3K27 demethylase UTX, a complex-specific subunit of the enhancer-associated MLL3/4 complexes, and MiDAC. We demonstrate that UTX bridges the association of the MLL3/4 complexes and MiDAC by interacting with ELMSAN1, a scaffolding subunit of MiDAC. Our data shows that MiDAC constitutes a negative genome-wide regulator of H4K20ac, an activity which is counteracted by the MLL3/4 complexes. MiDAC and the MLL3/4 complexes co-localize at many genomic regions, that are enriched for H4K20ac and the enhancer marks H3K4me1, H3K4me2 and H3K27ac. We find that MiDAC antagonizes the recruitment of the MLL3/4 complexes to negatively regulate H4K20ac, H3K4me2 and H3K27ac resulting in transcriptional attenuation of associated genes. In summary, our findings provide a paradigm how the opposing roles of chromatin-modifying components, such as MiDAC and the MLL3/4 complexes, balance the transcriptional output of specific gene expression programs.

scholarly journals Distinct CoREST complexes act in a cell-type-specific manner

2019 ◽  
Author(s):  
Igor Mačinković ◽  
Ina Theofel ◽  
Tim Hundertmark ◽  
Kristina Kovač ◽  
Stephan Awe ◽  
...  
Keyword(s):  
Gene Expression ◽  
Germ Line ◽  
Protein Complexes ◽  
Specific Gene ◽  
S2 Cells ◽  
Cell Type ◽  
Specific Gene Expression ◽  
Genome Wide ◽  
A Cell ◽  
Cell Type Specific

Abstract CoREST has been identified as a subunit of several protein complexes that generate transcriptionally repressive chromatin structures during development. However, a comprehensive analysis of the CoREST interactome has not been carried out. We use proteomic approaches to define the interactomes of two dCoREST isoforms, dCoREST-L and dCoREST-M, in Drosophila. We identify three distinct histone deacetylase complexes built around a common dCoREST/dRPD3 core: A dLSD1/dCoREST complex, the LINT complex and a dG9a/dCoREST complex. The latter two complexes can incorporate both dCoREST isoforms. By contrast, the dLSD1/dCoREST complex exclusively assembles with the dCoREST-L isoform. Genome-wide studies show that the three dCoREST complexes associate with chromatin predominantly at promoters. Transcriptome analyses in S2 cells and testes reveal that different cell lineages utilize distinct dCoREST complexes to maintain cell-type-specific gene expression programmes: In macrophage-like S2 cells, LINT represses germ line-related genes whereas other dCoREST complexes are largely dispensable. By contrast, in testes, the dLSD1/dCoREST complex prevents transcription of germ line-inappropriate genes and is essential for spermatogenesis and fertility, whereas depletion of other dCoREST complexes has no effect. Our study uncovers three distinct dCoREST complexes that function in a lineage-restricted fashion to repress specific sets of genes thereby maintaining cell-type-specific gene expression programmes.

scholarly journals Genome-wide comparison of allele-specific gene expression between African and European populations

2018 ◽  
Vol 27 (6) ◽  
pp. 1067-1077 ◽  
Author(s):  
Lei Tian ◽  
Asifullah Khan ◽  
Zhilin Ning ◽  
Kai Yuan ◽  
Chao Zhang ◽  
...  
Keyword(s):  
Gene Expression ◽  
Specific Gene ◽  
Specific Gene Expression ◽  
Genome Wide ◽  
Allele Specific ◽  
European Populations

scholarly journals Transcriptome analysis of Plasmodium berghei during exo-erythrocytic development

2019 ◽  
Author(s):  
Reto Caldelari ◽  
Sunil Dogga ◽  
Marc W. Schmid ◽  
Blandine Franke-Fayard ◽  
Chris J Janse ◽  
...  
Keyword(s):  
Gene Expression ◽  
Life Cycle ◽  
Plasmodium Berghei ◽  
Expression Profiles ◽  
Specific Gene ◽  
Rna Seq ◽  
Erythrocytic Stage ◽  
Liver Stage ◽  
Specific Gene Expression ◽  
Genome Wide

SummaryThe complex life cycle of malaria parasites requires well-orchestrated stage specific gene expression. In the vertebrate host the parasites grow and multiply by schizogony in two different environments: within erythrocytes and within hepatocytes. Whereas erythrocytic parasites are rather well-studied in this respect, relatively little is known about the exo-erythrocytic stages. In an attempt to fill this gap, we performed genome wide RNA-seq analyses of various exo-erythrocytic stages of Plasmodium berghei including sporozoites, samples from a time-course of liver stage development and detached cells, which contain infectious merozoites and represent the final step in exo-erythrocytic development. The analysis represents the completion of the transcriptome of the entire life cycle of P. berghei parasites with temporal detailed analysis of the liver stage allowing segmentation of the transcriptome across the progression of the life cycle. We have used these RNA-seq data from different developmental stages to cluster genes with similar expression profiles, in order to infer their functions. A comparison with published data of other parasite stages confirmed stage-specific gene expression and revealed numerous genes that are expressed differentially in blood and exo-erythrocytic stages. One of the most exo-erythrocytic stage-specific genes was PBANKA_1003900, which has previously been annotated as a “gametocyte specific protein”. The promoter of this gene drove high GFP expression in exo-erythrocytic stages, confirming its expression profile seen by RNA-seq. The comparative analysis of the genome wide mRNA expression profiles of erythrocytic and different exo-erythrocytic stages improves our understanding of gene regulation of Plasmodium parasites and can be used to model exo-erythrocytic stage metabolic networks and identify differences in metabolic processes during schizogony in erythrocytes and hepatocytes.

scholarly journals Transcriptome analysis of Plasmodium berghei during exo-erythrocytic development

2019 ◽  
Vol 18 (1) ◽  
Author(s):  
Reto Caldelari ◽  
Sunil Dogga ◽  
Marc W. Schmid ◽  
Blandine Franke-Fayard ◽  
Chris J. Janse ◽  
...  
Keyword(s):  
Gene Expression ◽  
Life Cycle ◽  
Plasmodium Berghei ◽  
Expression Profiles ◽  
Specific Gene ◽  
Rna Seq ◽  
Erythrocytic Stage ◽  
Liver Stage ◽  
Specific Gene Expression ◽  
Genome Wide

Abstract Background The complex life cycle of malaria parasites requires well-orchestrated stage specific gene expression. In the vertebrate host the parasites grow and multiply by schizogony in two different environments: within erythrocytes and within hepatocytes. Whereas erythrocytic parasites are well-studied in this respect, relatively little is known about the exo-erythrocytic stages. Methods In an attempt to fill this gap, genome wide RNA-seq analyses of various exo-erythrocytic stages of Plasmodium berghei including sporozoites, samples from a time-course of liver stage development and detached cells were performed. These latter contain infectious merozoites and represent the final step in exo-erythrocytic development. Results The analysis represents the complete transcriptome of the entire life cycle of P. berghei parasites with temporal detailed analysis of the liver stage allowing comparison of gene expression across the progression of the life cycle. These RNA-seq data from different developmental stages were used to cluster genes with similar expression profiles, in order to infer their functions. A comparison with published data from other parasite stages confirmed stage-specific gene expression and revealed numerous genes that are expressed differentially in blood and exo-erythrocytic stages. One of the most exo-erythrocytic stage-specific genes was PBANKA_1003900, which has previously been annotated as a “gametocyte specific protein”. The promoter of this gene drove high GFP expression in exo-erythrocytic stages, confirming its expression profile seen by RNA-seq. Conclusions The comparative analysis of the genome wide mRNA expression profiles of erythrocytic and different exo-erythrocytic stages could be used to improve the understanding of gene regulation in Plasmodium parasites and can be used to model exo-erythrocytic stage metabolic networks toward the identification of differences in metabolic processes during schizogony in erythrocytes and hepatocytes.

scholarly journals Changes in DNA Methylation in Response to 6-Benzylaminopurine Affect Allele-Specific Gene Expression in Populus tomentosa

2020 ◽  
Author(s):  
Anran Xuan ◽  
Yuepeng Song ◽  
Chenhao Bu ◽  
Panfei Chen ◽  
Yousry A. El-Kassaby ◽  
...  
Keyword(s):  
Gene Expression ◽  
Dna Methylation ◽  
Expression Patterns ◽  
Populus Tomentosa ◽  
Differentially Expressed ◽  
Specific Gene ◽  
Snp Analysis ◽  
Specific Gene Expression ◽  
Genome Wide ◽  
Allele Specific

The cytokinins play important roles in plant growth and development by regulating gene expression at genome wide level. DNA methylation is responsive to the external environment, but whether DNA methylation changes in response to cytokinin treatment to regulate gene expression is still unclear. Here, we used bisulfite sequencing and RNA sequencing to examine genome-wide DNA methylation and gene expression patterns in poplar (Populus tomentosa) after treatment with the synthetic cytokinin 6-benzylaminopurine (6-BA). We identified 566 significantly differentially methylated regions (DMRs) in response to 6-BA treatment. Transcriptome analysis showed that 501 protein-coding genes, 262 long non-coding RNAs, and 15,793 24-nt small interfering RNAs were differentially expressed under 6-BA treatment. Among these, 79% were differentially expressed between alleles in P. tomentosa. Combined DNA methylation and gene expression analysis demonstrated that DNA methylation plays an important role in regulating allele-specific gene expression. To further investigate the relationship between these 6-BA-responsive genes and phenotypic variation, we performed SNP analysis of 507 6-BA-responsive DMRs via re-sequencing using a natural population of P. tomentosa and identified 206 SNPs that were significantly associated with growth and wood properties. Association analysis indicated that 53% of loci with allele-specific expression had primarily dominant effects on poplar traits. Our comprehensive analyses of P. tomentosa DNA methylation and the regulation of allele-specific gene expression suggest that DNA methylation is an important regulator of imbalanced expression between allelic loci.

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