scholarly journals Tramtrack acts during late pupal development to direct ant caste identity

PLoS Genetics ◽  
2021 ◽  
Vol 17 (9) ◽  
pp. e1009801
Author(s):  
Karl M. Glastad ◽  
Linyang Ju ◽  
Shelley L. Berger

A key question in the rising field of neuroepigenetics is how behavioral plasticity is established and maintained in the developing CNS of multicellular organisms. Behavior is controlled through systemic changes in hormonal signaling, cell-specific regulation of gene expression, and changes in neuronal connections in the nervous system, however the link between these pathways is unclear. In the ant Camponotus floridanus, the epigenetic corepressor CoREST is a central player in experimentally-induced reprogramming of caste-specific behavior, from soldier (Major worker) to forager (Minor worker). Here, we show this pathway is engaged naturally on a large genomic scale during late pupal development targeting multiple genes differentially expressed between castes, and central to this mechanism is the protein tramtrack (ttk), a DNA binding partner of CoREST. Caste-specific differences in DNA binding of ttk co-binding with CoREST correlate with caste-biased gene expression both in the late pupal stage and immediately after eclosion. However, we find a unique set of exclusive Minor-bound genes that show ttk pre-binding in the late pupal stage preceding CoREST binding, followed by caste-specific gene repression on the first day of eclosion. In addition, we show that ttk binding correlates with neurogenic Notch signaling, and that specific ttk binding between castes is enriched for regulatory sites associated with hormonal function. Overall our findings elucidate a pathway of transcription factor binding leading to a repressive epigenetic axis that lies at the crux of development and hormonal signaling to define worker caste identity in C. floridanus.

Reproduction ◽  
2016 ◽  
pp. R91-R99 ◽  
Author(s):  
Petra Sipilä ◽  
Ida Björkgren

The epididymis is necessary for post-testicular sperm maturation. During their epididymal transit, spermatozoa gain ability for progressive movement and fertilization. The epididymis is composed of several segments that have distinct gene expression profiles that enable the establishment of the changing luminal environment required for sperm maturation. The epididymal gene expression is regulated by endocrine, lumicrine, and paracrine factors in a segment-specific manner. Thus, in addition to its importance for male fertility, the epididymis is a valuable model tissue for studying the regulation of gene expression. This review concentrates on recent advances in understanding the androgen, small RNA, and epigenetically mediated regulation of segment-specific gene expression in the epididymis.


2020 ◽  
Author(s):  
Eilidh Carrington ◽  
Roel H. M. Cooijmans ◽  
Dominique Keller ◽  
Christa G. Toenhake ◽  
Richárd Bártfai ◽  
...  

AbstractMalaria parasites undergo a highly complex life cycle in the human host and the mosquito vector. The ApiAP2 family of sequence-specific DNA-binding proteins plays a dominant role in parasite development and life cycle progression. Of the ApiAP2 factors studied to date, most act as transcription factors regulating stage-specific gene expression. Here, we characterised a new ApiAP2 factor in Plasmodium falciparum (PF3D7_1456000) that we termed PfAP2-HC. Via detailed investigation of several single or double genetically engineered parasite lines, we demonstrate that PfAP2-HC specifically binds to heterochromatin throughout the genome. Intriguingly, PfAP2-HC does not bind DNA in vivo and recruitment of PfAP2-HC to heterochromatin is independent of its DNA-binding domain but strictly dependent on heterochromatin protein 1. Furthermore, our results suggest that PfAP2-HC functions neither in the regulation of gene expression nor in heterochromatin formation or maintenance. In summary, our findings reveal that PfAP2-HC constitutes a core component of heterochromatin in malaria parasites. They furthermore identify unexpected properties of ApiAP2 factors and suggest substantial functional divergence among the members of this important family of regulatory proteins.


2021 ◽  
Author(s):  
Biplabendu Das ◽  
Charissa de Bekker

AbstractBackgroundCircadian clocks allow organisms to anticipate daily fluctuations in their environment by driving rhythms in physiology and behavior. Inter-organismal differences in daily rhythms, called chronotypes, exist and can shift with age. In ants, age, caste-related behavior and chronotype appear to be linked. “Around-the-clock” active nurse ants are usually younger and, with age, transition into rhythmically active foragers. Moreover, ants can shift between these behavioral castes depending on social context. We investigated how changes in daily gene expression could be contributing to such behavioral plasticity in Camponotus floridanus carpenter ants by combining time-course behavioral assays and RNA-Sequencing of forager and nurse brains.ResultsWe found that nurse brains have three times fewer 24h oscillating genes than foragers. However, several hundred genes that oscillated every 24h in forager brains showed robust 8h oscillations in nurses, including the core clock genes Period and Shaggy. These differentially rhythmic genes consisted of several components of the circadian entrainment pathway, and showed enrichments for functions related to metabolism, cellular communication and protein modification. We additionally found that Vitellogenin, known to regulate division of labor in social insects, showed robust 24h oscillations in nurse brains but not in foragers. Furthermore, the protein products of several genes that were differentially expressed between the two ant castes were previously found in the trophallactic fluid of C. floridanus. This suggests a putative role for trophallaxis in regulating behavioral division of labor through caste-specific gene expression.ConclusionWe provide a first look at the chronobiological differences in gene expression between forager and nurse ant brains. This endeavor allowed us to identify putative molecular mechanisms underlying plastic timekeeping. Several components of the ant circadian clock and its output can seemingly oscillate at different harmonics of the circadian rhythm. We propose that such chronobiological plasticity has evolved to allow for distinct regulatory networks that underlie behavioral castes, while supporting swift caste transitions in response to colony demands. Behavioral division of labor is common among social insects. The links between chronobiological and behavioral plasticity that we found in C. floridanus, thus, likely represent a more general phenomenon that warrants further investigation.


Cells ◽  
2020 ◽  
Vol 9 (10) ◽  
pp. 2152
Author(s):  
Robin Loesch ◽  
Linda Chenane ◽  
Sabine Colnot

Chromatin remodelers are found highly mutated in cancer including hepatocellular carcinoma. These mutations frequently occur in ARID (AT-rich Interactive Domain) genes, encoding subunits of the ATP-dependent SWI/SNF remodelers. The increasingly prevalent complexity that surrounds the functions and specificities of the highly modular BAF (BG1/BRM-associated factors) and PBAF (polybromo-associated BAF) complexes, including ARID1A/B or ARID2, is baffling. The involvement of the SWI/SNF complexes in diverse tissues and processes, and especially in the regulation of gene expression, multiplies the specific outcomes of specific gene alterations. A better understanding of the molecular consequences of specific mutations impairing chromatin remodelers is needed. In this review, we summarize what we know about the tumor-modulating properties of ARID2 in hepatocellular carcinoma.


2015 ◽  
Vol 2015 ◽  
pp. 1-20 ◽  
Author(s):  
Hiroshi Kondo ◽  
Keiko Miyoshi ◽  
Shoji Sakiyama ◽  
Akira Tangoku ◽  
Takafumi Noma

Stem cell therapy appears to be promising for restoring damaged or irreparable lung tissue. However, establishing a simple and reproducible protocol for preparing lung progenitor populations is difficult because the molecular basis for alveolar epithelial cell differentiation is not fully understood. We investigated anin vitrosystem to analyze the regulatory mechanisms of alveolus-specific gene expression using a human alveolar epithelial type II (ATII) cell line, A549. After cloning A549 subpopulations, each clone was classified into five groups according to cell morphology and marker gene expression. Two clones (B7 and H12) were further analyzed. Under serum-free culture conditions,surfactant protein C(SPC), an ATII marker, was upregulated in both H12 and B7.Aquaporin 5(AQP5), an ATI marker, was upregulated in H12 and significantly induced in B7. When the RAS/MAPK pathway was inhibited,SPCandthyroid transcription factor-1(TTF-1) expression levels were enhanced. After treatment with dexamethasone (DEX), 8-bromoadenosine 3′5′-cyclic monophosphate (8-Br-cAMP), 3-isobutyl-1-methylxanthine (IBMX), and keratinocyte growth factor (KGF),surfactant protein BandTTF-1expression levels were enhanced. We found that A549-derived clones have plasticity in gene expression of alveolar epithelial differentiation markers and could be useful in studying ATII maintenance and differentiation.


2020 ◽  
Vol 3 (1) ◽  
Author(s):  
Ana J. Chucair-Elliott ◽  
Sarah R. Ocañas ◽  
David R. Stanford ◽  
Victor A. Ansere ◽  
Kyla B. Buettner ◽  
...  

AbstractEpigenetic regulation of gene expression occurs in a cell type-specific manner. Current cell-type specific neuroepigenetic studies rely on cell sorting methods that can alter cell phenotype and introduce potential confounds. Here we demonstrate and validate a Nuclear Tagging and Translating Ribosome Affinity Purification (NuTRAP) approach for temporally controlled labeling and isolation of ribosomes and nuclei, and thus RNA and DNA, from specific central nervous system cell types. Analysis of gene expression and DNA modifications in astrocytes or microglia from the same animal demonstrates differential usage of DNA methylation and hydroxymethylation in CpG and non-CpG contexts that corresponds to cell type-specific gene expression. Application of this approach in LPS treated mice uncovers microglia-specific transcriptome and epigenome changes in inflammatory pathways that cannot be detected with tissue-level analysis. The NuTRAP model and the validation approaches presented can be applied to any brain cell type for which a cell type-specific cre is available.


Blood ◽  
2019 ◽  
Vol 134 (24) ◽  
pp. 2195-2208 ◽  
Author(s):  
Daniel Sasca ◽  
Haiyang Yun ◽  
George Giotopoulos ◽  
Jakub Szybinski ◽  
Theo Evan ◽  
...  

Cohesin mutations are common in myeloid malignancy. Sasca et al elucidate the potential role of cohesin loss in myelodysplastic syndrome and acute myeloid leukemia (MDS/AML). They demonstrate that cohesin binding is critical for erythroid-specific gene expression and that reduction in cohesin impairs terminal erythroid maturation and promotes myeloid malignancy.


2020 ◽  
Vol 38 (1) ◽  
pp. 397-419
Author(s):  
Michael J. Shapiro ◽  
Virginia Smith Shapiro

T cell development involves stepwise progression through defined stages that give rise to multiple T cell subtypes, and this is accompanied by the establishment of stage-specific gene expression. Changes in chromatin accessibility and chromatin modifications accompany changes in gene expression during T cell development. Chromatin-modifying enzymes that add or reverse covalent modifications to DNA and histones have a critical role in the dynamic regulation of gene expression throughout T cell development. As each chromatin-modifying enzyme has multiple family members that are typically all coexpressed during T cell development, their function is sometimes revealed only when two related enzymes are concurrently deleted. This work has also revealed that the biological effects of these enzymes often involve regulation of a limited set of targets. The growing diversity in the types and sites of modification, as well as the potential for a single enzyme to catalyze multiple modifications, is also highlighted.


2015 ◽  
Vol 197 (7) ◽  
pp. 1197-1207 ◽  
Author(s):  
Guangze Jin ◽  
Martin S. Pavelka ◽  
J. Scott Butler

ABSTRACTBacterial toxin-antitoxin systems play a critical role in the regulation of gene expression, leading to developmental changes, reversible dormancy, and cell death. Type II toxin-antitoxin pairs, composed of protein toxins and antitoxins, exist in nearly all bacteria and are classified into six groups on the basis of the structure of the toxins. The VapBC group comprises the most common type II system and, like other toxin-antitoxin systems, functions to elicit dormancy by inhibiting protein synthesis. Activation of toxin function requires protease degradation of the VapB antitoxin, which frees the VapC toxin from the VapBC complex, allowing it to hydrolyze the RNAs required for translation. Generally, type II antitoxins bind with high specificity to their cognate toxins via a toxin-binding domain and endow the complex with DNA-binding specificity via a DNA-binding domain. Despite the ubiquity of VapBC systems and their critical role in the regulation of gene expression, few functional studies have addressed the details of VapB-VapC interactions. Here we report on the results of experiments designed to identify molecular determinants of the specificity of theMycobacterium tuberculosisVapB4 antitoxin for its cognate VapC4 toxin. The results identify the minimal domain of VapB4 required for this interaction as well as the amino acid side chains required for binding to VapC4. These findings have important implications for the evolution of VapBC toxin-antitoxin systems and their potential as targets of small-molecule protein-protein interaction inhibitors.IMPORTANCEVapBC toxin-antitoxin pairs are the most widespread type II toxin-antitoxin systems in bacteria, where they are thought to play key roles in stress-induced dormancy and the formation of persisters. The VapB antitoxins are critical to these processes because they inhibit the activity of the toxins and provide the DNA-binding specificity that controls the synthesis of both proteins. Despite the importance of VapB antitoxins and the existence of several VapBC crystal structures, little is known about their functional featuresin vivo. Here we report the findings of the first comprehensive structure-function analysis of a VapB toxin. The results identify the minimal toxin-binding domain, its modular antitoxin function, and the specific amino acid side chains required for its activity.


1998 ◽  
Vol 330 (1) ◽  
pp. 335-343 ◽  
Author(s):  
M. Bahaa FADEL ◽  
C. Stephane BOUTET ◽  
Thomas QUERTERMOUS

To investigate the molecular basis of endothelial cell-specific gene expression, we have examined the DNA sequences and the cognate DNA-binding proteins that mediate transcription of the murine tie2/tek gene. Reporter transfection experiments conformed with earlier findings in transgenic mice, indicating that the upstream promoter of Tie2/Tek is capable of activating transcription in an endothelial cell-specific fashion. These experiments have also allowed the identification of a single upstream inhibitory region (region I) and two positive regulatory regions (regions U and A) in the proximal promoter. Electrophoretic mobility-shift assays have allowed further characterization of three novel DNA-binding sequences associated with these regions and have provided preliminary characterization of the protein factors binding to these elements. Two of the elements (U and A) confer increased transcription on a heterologous promoter, with element U functioning in an endothelial-cell-selective manner. By employing embryonic endothelial-like yolk sac cells in parallel with adult-derived endothelial cells, we have identified differences in functional activity and protein binding that may reflect mechanisms for specifying developmental regulation of tie2/tek expression. Further study of the DNA and protein elements characterized in these experiments is likely to provide new insight into the molecular basis of developmental- and cell-specific gene expression in the endothelium.


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