scholarly journals Hierarchical transcriptional control regulatesPlasmodium falciparumsexual differentiation

2019 ◽  
Author(s):  
Riëtte van Biljon ◽  
Roelof van Wyk ◽  
Heather J. Painter ◽  
Lindsey Orchard ◽  
Janette Reader ◽  
...  

AbstractMalaria pathogenesis relies on sexual gametocyte forms of the malaria parasite to be transmitted between the infected human and the mosquito host but the molecular mechanisms controlling gametocytogenesis remains poorly understood. Here we provide a high-resolution transcriptome ofPlasmodium falciparumas it commits to and develops through gametocytogenesis. The gametocyte-associated transcriptome is significantly different from that of the asexual parasites, with dynamic gene expression shifts characterizing early, intermediate and late-stage gametocyte development and results in differential timing for sex-specific transcripts. The striking transcriptional dynamics suggest strict transcriptional control during gametocytogenesis inP. falciparum, which we propose is mediated by putative regulators including epigenetic mechanisms (driving active repression of proliferation-associated processes) and a cascade-like expression of ApiAP2 transcription factors. The gametocyte transcriptome serves as the blueprint for sexual differentiation and will be a rich resource for future functional studies on this critical stage ofPlasmodiumdevelopment, as the intraerythrocytic transcriptome has been for our understanding of the asexual cycle.

Author(s):  
Riëtte van Biljon ◽  
Roelof van Wyk ◽  
Heather J. Painter ◽  
Lindsey Orchard ◽  
Janette Reader ◽  
...  

Abstract Background Malaria pathogenesis relies on sexual gametocyte forms of the malaria parasite to be transmitted between the infected human and the mosquito host but the molecular mechanisms controlling gametocytogenesis remains poorly understood. Here we provide a high-resolution transcriptome of Plasmodium falciparum as it commits to and develops through gametocytogenesis. Results The gametocyte-associated transcriptome is significantly different from that of the asexual parasites, with dynamic gene expression shifts characterizing early, intermediate and late-stage gametocyte development and results in differential timing for sex-specific transcripts. The transcriptional dynamics suggest strict transcriptional control during gametocytogenesis in P. falciparum, which we propose is mediated by putative regulators including epigenetic mechanisms (driving active repression of proliferation-associated processes) and a cascade-like expression of ApiAP2 transcription factors. Conclusions The gametocyte transcriptome serves as the blueprint for sexual differentiation and will be a rich resource for future functional studies on this critical stage of Plasmodium development, as the intraerythrocytic transcriptome has been for our understanding of the asexual cycle.


BMC Genomics ◽  
2019 ◽  
Vol 20 (1) ◽  
Author(s):  
Riëtte van Biljon ◽  
Roelof van Wyk ◽  
Heather J. Painter ◽  
Lindsey Orchard ◽  
Janette Reader ◽  
...  

Abstract Background Malaria pathogenesis relies on sexual gametocyte forms of the malaria parasite to be transmitted between the infected human and the mosquito host but the molecular mechanisms controlling gametocytogenesis remains poorly understood. Here we provide a high-resolution transcriptome of Plasmodium falciparum as it commits to and develops through gametocytogenesis. Results The gametocyte-associated transcriptome is significantly different from that of the asexual parasites, with dynamic gene expression shifts characterizing early, intermediate and late-stage gametocyte development and results in differential timing for sex-specific transcripts. The transcriptional dynamics suggest strict transcriptional control during gametocytogenesis in P. falciparum, which we propose is mediated by putative regulators including epigenetic mechanisms (driving active repression of proliferation-associated processes) and a cascade-like expression of ApiAP2 transcription factors. Conclusions The gametocyte transcriptome serves as the blueprint for sexual differentiation and will be a rich resource for future functional studies on this critical stage of Plasmodium development, as the intraerythrocytic transcriptome has been for our understanding of the asexual cycle.


2019 ◽  
Author(s):  
Riëtte van Biljon ◽  
Roelof van Wyk ◽  
Heather J. Painter ◽  
Lindsey Orchard ◽  
Janette Reader ◽  
...  

Abstract Background: Malaria pathogenesis relies on sexual gametocyte forms of the malaria parasite to be transmitted between the infected human and the mosquito host but the molecular mechanisms controlling gametocytogenesis remains poorly understood. Here we provide a high-resolution transcriptome of Plasmodium falciparum as it commits to and develops through gametocytogenesis. Results : The gametocyte-associated transcriptome is significantly different from that of the asexual parasites, with dynamic gene expression shifts characterizing early, intermediate and late-stage gametocyte development and results in differential timing for sex-specific transcripts. The transcriptional dynamics suggest strict transcriptional control during gametocytogenesis in P. falciparum, which we propose is mediated by putative regulators including epigenetic mechanisms (driving active repression of proliferation-associated processes) and a cascade-like expression of ApiAP2 transcription factors. Conclusions : The gametocyte transcriptome serves as the blueprint for sexual differentiation and will be a rich resource for future functional studies on this critical stage of Plasmodium development, as the intraerythrocytic transcriptome has been for our understanding of the asexual cycle.


2019 ◽  
Author(s):  
Riëtte van Biljon ◽  
Roelof van Wyk ◽  
Heather J. Painter ◽  
Lindsey Orchard ◽  
Janette Reader ◽  
...  

Abstract Background: Malaria pathogenesis relies on sexual gametocyte forms of the malaria parasite to be transmitted between the infected human and the mosquito host but the molecular mechanisms controlling gametocytogenesis remains poorly understood. Here we provide a high-resolution transcriptome of Plasmodium falciparum as it commits to and develops through gametocytogenesis. Results : The gametocyte-associated transcriptome is significantly different from that of the asexual parasites, with dynamic gene expression shifts characterizing early, intermediate and late-stage gametocyte development and results in differential timing for sex-specific transcripts. The transcriptional dynamics suggest strict transcriptional control during gametocytogenesis in P. falciparum, which we propose is mediated by putative regulators including epigenetic mechanisms (driving active repression of proliferation-associated processes) and a cascade-like expression of ApiAP2 transcription factors. Conclusions : The gametocyte transcriptome serves as the blueprint for sexual differentiation and will be a rich resource for future functional studies on this critical stage of Plasmodium development, as the intraerythrocytic transcriptome has been for our understanding of the asexual cycle.


2021 ◽  
Vol 7 (9) ◽  
pp. eabd7974
Author(s):  
Michela Serresi ◽  
Sonia Kertalli ◽  
Lifei Li ◽  
Matthias Jürgen Schmitt ◽  
Yuliia Dramaretska ◽  
...  

Epithelial-mesenchymal transition (EMT) is a developmental process hijacked by cancer cells to modulate proliferation, migration, and stress response. Whereas kinase signaling is believed to be an EMT driver, the molecular mechanisms underlying epithelial-mesenchymal interconversion are incompletely understood. Here, we show that the impact of chromatin regulators on EMT interconversion is broader than that of kinases. By combining pharmacological modulation of EMT, synthetic genetic tracing, and CRISPR interference screens, we uncovered a minority of kinases and several chromatin remodelers, writers, and readers governing homeostatic EMT in lung cancer cells. Loss of ARID1A, DOT1L, BRD2, and ZMYND8 had nondeterministic and sometimes opposite consequences on epithelial-mesenchymal interconversion. Together with RNAPII and AP-1, these antagonistic gatekeepers control chromatin of active enhancers, including pan-cancer-EMT signature genes enabling supraclassification of anatomically diverse tumors. Thus, our data uncover general principles underlying transcriptional control of cancer cell plasticity and offer a platform to systematically explore chromatin regulators in tumor-state–specific therapy.


Parasitology ◽  
2000 ◽  
Vol 121 (2) ◽  
pp. 127-133 ◽  
Author(s):  
T. G. SMITH ◽  
P. LOURENÇO ◽  
R. CARTER ◽  
D. WALLIKER ◽  
L. C. RANFORD-CARTWRIGHT

2021 ◽  
Vol 22 (13) ◽  
pp. 7029
Author(s):  
Cai-Yun Xiong ◽  
Qing-You Gong ◽  
Hu Pei ◽  
Chang-Jian Liao ◽  
Rui-Chun Yang ◽  
...  

In maize, the ear shank is a short branch that connects the ear to the stalk. The length of the ear shank mainly affects the transportation of photosynthetic products to the ear, and also influences the dehydration of the grain by adjusting the tightness of the husks. However, the molecular mechanisms of maize shank elongation have rarely been described. It has been reported that the maize ear shank length is a quantitative trait, but its genetic basis is still unclear. In this study, RNA-seq was performed to explore the transcriptional dynamics and determine the key genes involved in maize shank elongation at four different developmental stages. A total of 8145 differentially expressed genes (DEGs) were identified, including 729 transcription factors (TFs). Some important genes which participate in shank elongation were detected via function annotation and temporal expression pattern analyses, including genes related to signal transduction hormones (auxin, brassinosteroids, gibberellin, etc.), xyloglucan and xyloglucan xyloglucosyl transferase, and transcription factor families. The results provide insights into the genetic architecture of maize ear shanks and developing new varieties with ideal ear shank lengths, enabling adjustments for mechanized harvesting in the future.


1985 ◽  
Vol 5 (6) ◽  
pp. 1295-1300
Author(s):  
Y Barra ◽  
K Tanaka ◽  
K J Isselbacher ◽  
G Khoury ◽  
G Jay

The identification of a unique major histocompatibility complex class I gene, designated Q10, which encodes a secreted rather than a cell surface antigen has led to questions regarding its potential role in regulating immunological functions. Since the Q10 gene is specifically activated only in the liver, we sought to define the molecular mechanisms which control its expression in a tissue-specific fashion. Results obtained by transfection of the cloned Q10 gene, either in the absence or presence of a heterologous transcriptional enhancer, into a variety of cell types of different tissue derivations are consistent with the Q10 gene being regulated at two levels. The first is by a cis-dependent mechanism which appears to involve site-specific DNA methylation. The second is by a trans-acting mechanism which would include the possibility of an enhancer binding factor. The ability to efficiently express the Q10 gene in certain transfected cell lines offers an opportunity to obtain this secreted class I antigen in quantities sufficient for functional studies; this should also make it possible to define regulatory sequences which may be responsible for the tissue-specific expression of Q10.


Sarcoma ◽  
2011 ◽  
Vol 2011 ◽  
pp. 1-5 ◽  
Author(s):  
Krithi Rao-Bindal ◽  
Eugenie S. Kleinerman

The role of genetic mutations in the development of osteosarcoma, such as alterations in p53 and Rb, is well understood. However, the significance of epigenetic mechanisms in the progression of osteosarcoma remains unclear and is increasingly being investigated. Recent evidence suggests that epigenetic alterations such as methylation and histone modifications of genes involved in cell cycle regulation and apoptosis may contribute to the pathogenesis of this tumor. Importantly, understanding the molecular mechanisms of regulation of these pathways may give insight into novel therapeutic strategies for patients with osteosarcoma. This paper serves to summarize the described epigenetic mechanisms in the tumorigenesis of osteosarcoma, specifically those pertaining to apoptosis and cell cycle regulation.


2016 ◽  
Vol 371 (1688) ◽  
pp. 20150114 ◽  
Author(s):  
Nancy G. Forger

Circumstantial evidence alone argues that the establishment and maintenance of sex differences in the brain depend on epigenetic modifications of chromatin structure. More direct evidence has recently been obtained from two types of studies: those manipulating a particular epigenetic mechanism, and those examining the genome-wide distribution of specific epigenetic marks. The manipulation of histone acetylation or DNA methylation disrupts the development of several neural sex differences in rodents. Taken together, however, the evidence suggests there is unlikely to be a simple formula for masculine or feminine development of the brain and behaviour; instead, underlying epigenetic mechanisms may vary by brain region or even by dependent variable within a region. Whole-genome studies related to sex differences in the brain have only very recently been reported, but suggest that males and females may use different combinations of epigenetic modifications to control gene expression, even in cases where gene expression does not differ between the sexes. Finally, recent findings are discussed that are likely to direct future studies on the role of epigenetic mechanisms in sexual differentiation of the brain and behaviour.


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