Comparative epigenomics in the Brassicaceae reveals two evolutionarily conserved modes of PRC2-mediated gene regulation

Abstract Recent unbiased exome and whole-genome sequencing studies have identified ARID1B (originally BAF250b) as the most frequently mutated gene in human de novo neurodevelopmental disorders and a high confidence autism gene. ARID1B is a subunit of the multimeric SWI/SNF or Brg/Brahma-Associated Factor (BAF) ATP-dependent chromatin remodeling complex. Studies of Arid1b+/- mice as well as other BAF subunit mutants have found defects in neural progenitor proliferation and activity-dependent neuronal dendritogenesis; however, to date, the molecular impact of ARID1B mutations on the human neural lineage has not been investigated. Remarkably, ARID1B is required for expression of HOX genes, including anterior HOX genes necessary for brain development. Despite the high homology with ARID1A and the fact that ARID1A is expressed at about 3-fold higher levels, it is unable to compensate for heterozygous loss of ARID1B. These changes in gene expression were paralleled by dosage-sensitive altered deposition of histone H3 lysine-27 trimethylation (H3K27me3) and histone H2A lysine-119 ubiquitination (H2AK119ub) indicating that an evolutionarily conserved pathway of HOX gene regulation underlies the neurodevelopmental defects accompanying ARID1B haploinsufficiency. Using FIRE-Cas9, we show that the unmutated ARID1B allele can be activated to near normal and potentially therapeutic levels.

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The evolutionary acquisition and mode of functions of promoter-associated non-coding RNAs (pancRNAs) for mammalian development

Essays in Biochemistry ◽

10.1042/ebc20200143 ◽

2021 ◽

Author(s):

Boyang An ◽

Tomonori Kameda ◽

Takuya Imamura

Keyword(s):

Gene Regulation ◽

Neural Differentiation ◽

Single Copy ◽

Research Progress ◽

Mammalian Development ◽

Comparative Epigenomics ◽

Specific Manner ◽

A Cell ◽

Non Coding Rnas ◽

Mammalian Embryonic Development

Abstract Increasing evidence has shown that many long non-coding RNAs (lncRNAs) are involved in gene regulation in a variety of ways such as transcriptional, post-transcriptional and epigenetic regulation. Promoter-associated non-coding RNAs (pancRNAs), which are categorized into the most abundant single-copy lncRNA biotype, play vital regulatory roles in finely tuning cellular specification at the epigenomic level. In short, pancRNAs can directly or indirectly regulate downstream genes to participate in the development of organisms in a cell-specific manner. In this review, we will introduce the evolutionarily acquired characteristics of pancRNAs as determined by comparative epigenomics and elaborate on the research progress on pancRNA-involving processes in mammalian embryonic development, including neural differentiation.

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SirA Orthologs Affect both Motility and Virulence

Journal of Bacteriology ◽

10.1128/jb.183.7.2249-2258.2001 ◽

2001 ◽

Vol 183 (7) ◽

pp. 2249-2258 ◽

Cited By ~ 75

Author(s):

Robert I. Goodier ◽

Brian M. M. Ahmer

Keyword(s):

Gene Regulation ◽

Response Regulator ◽

Virulence Gene ◽

Positive Control ◽

Evolutionarily Conserved ◽

Serovar Typhimurium ◽

Flagellar Regulon ◽

Regulatory Effects ◽

Virulence Gene Regulation ◽

Transcriptional Fusions

ABSTRACT The sirA gene of Salmonella entericaserovar Typhimurium encodes a two-component response regulator of the FixJ family that has a positive regulatory influence on the expression of type III secretion genes involved with epithelial cell invasion and the elicitation of bovine gastroenteritis. SirA orthologs inPseudomonas, Vibrio, and Erwinia control the expression of distinct virulence genes in these genera, but an evolutionarily conserved target of SirA regulation has never been identified. In this study we tested the hypothesis thatsirA may be an ancient member of the flagellar regulon. We examined the effect of a sirA mutation on transcriptional fusions to flagellar promoters (flhD, fliE, fliF, flgA, flgB, fliC, fliD, motA, and fliA) while using fusions to the virulence gene sopB as a positive control. SirA had only small regulatory effects on all fusions in liquid medium (less than fivefold). However, in various types of motility agar plates,sirA was able to activate a sopB fusion by up to 63-fold while repressing flagellar fusions by values exceeding 100-fold. Mutations in the sirA orthologs ofEscherichia coli, Vibrio cholerae, Pseudomonas fluorescens, and Pseudomonas aeruginosa result in defects in either motility or motility gene regulation, suggesting that control of flagellar regulons may be an evolutionarily conserved function ofsirA orthologs. The implications for our understanding of virulence gene regulation in the gamma Proteobacteria are discussed.

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Cohesin: a critical chromatin organizer in mammalian gene regulation

Biochemistry and Cell Biology ◽

10.1139/o11-039 ◽

2011 ◽

Vol 89 (5) ◽

pp. 445-458 ◽

Cited By ~ 11

Author(s):

Richard Chien ◽

Weihua Zeng ◽

Alexander R. Ball ◽

Kyoko Yokomori

Keyword(s):

Dna Repair ◽

Gene Regulation ◽

Cellular Differentiation ◽

Developmental Disorders ◽

Mitotic Chromosome ◽

Protein Complexes ◽

Chromatin Organization ◽

Genome Integrity ◽

Evolutionarily Conserved ◽

Functional Hierarchy

Cohesins are evolutionarily conserved essential multi-protein complexes that are important for higher-order chromatin organization. They play pivotal roles in the maintenance of genome integrity through mitotic chromosome regulation, DNA repair and replication, as well as gene regulation critical for proper development and cellular differentiation. In this review, we will discuss the multifaceted functions of mammalian cohesins and their apparent functional hierarchy in the cell, with particular focus on their actions in gene regulation and their relevance to human developmental disorders.

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MicroRNAs: Potentially important regulators for schistosome development and therapeutic targets against schistosomiasis

Parasitology ◽

10.1017/s0031182011001855 ◽

2012 ◽

Vol 139 (5) ◽

pp. 669-679 ◽

Cited By ~ 21

Author(s):

GUOFENG CHENG ◽

YOUXIN JIN

Keyword(s):

Gene Regulation ◽

Complex Life Cycle ◽

Current Status ◽

Biological Processes ◽

Messenger Rnas ◽

Regulate Gene Expression ◽

Rna Molecules ◽

Non Coding Rna ◽

Evolutionarily Conserved ◽

Multicellular Organisms

SUMMARYMicroRNAs (miRNAs) are small, endogenous non-coding RNA molecules that regulate gene expression post-transcriptionally by targeting the 3′ untranslated region (3′ UTR) of messenger RNAs. Since the discovery of the first miRNA in Caenorhabditis elegans, important regulatory roles for miRNAs in many key biological processes including development, cell proliferation, cell differentiation and apoptosis of many organisms have been described. Hundreds of miRNAs have been identified in various multicellular organisms and many are evolutionarily conserved. Schistosomes are multi-cellular eukaryotes with a complex life-cycle that require genes to be expressed and regulated precisely. Recently, miRNAs have been identified in two major schistosome species, Schistosoma japonicum and S. mansoni. These miRNAs are likely to play critical roles in schistosome development and gene regulation. Here, we review recent studies on schistosome miRNAs and discuss the potential roles of miRNAs in schistosome development and gene regulation. We also summarize the current status for targeting miRNAs and the potential of this approach for therapy against schistosomiasis.

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Apoptosis and development

Essays in Biochemistry ◽

10.1042/bse0390011 ◽

2003 ◽

Vol 39 ◽

pp. 11-24 ◽

Cited By ~ 6

Author(s):

Justin V McCarthy

Keyword(s):

Drosophila Melanogaster ◽

Mammalian Cells ◽

Cell Number ◽

Model Organisms ◽

Biological Processes ◽

Nematode Caenorhabditis Elegans ◽

Apoptotic Pathway ◽

Genetic Pathways ◽

Evolutionarily Conserved ◽

Multicellular Organisms

Apoptosis is an evolutionarily conserved process used by multicellular organisms to developmentally regulate cell number or to eliminate cells that are potentially detrimental to the organism. The large diversity of regulators of apoptosis in mammalian cells and their numerous interactions complicate the analysis of their individual functions, particularly in development. The remarkable conservation of apoptotic mechanisms across species has allowed the genetic pathways of apoptosis determined in lower species, such as the nematode Caenorhabditis elegans and the fruitfly Drosophila melanogaster, to act as models for understanding the biology of apoptosis in mammalian cells. Though many components of the apoptotic pathway are conserved between species, the use of additional model organisms has revealed several important differences and supports the use of model organisms in deciphering complex biological processes such as apoptosis.

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