scholarly journals Epigenetic Control and Cancer: The Potential of Histone Demethylases as Therapeutic Targets

2012 ◽  
Vol 5 (9) ◽  
pp. 963-990 ◽  
Author(s):  
Fernando Lizcano ◽  
Jeison Garcia
Keyword(s):  
Molecular Level ◽  
Expression Profiles ◽  
Gene Expression Profiles ◽  
Histone Demethylase ◽  
Point Of View ◽  
Histone Demethylases ◽  
Regulate Gene Expression ◽  
Number Of Factors ◽  
Demethylase Activity ◽  
Current Point

The development of cancer involves an immense number of factors at the molecular level. These factors are associated principally with alterations in the epigenetic mechanisms that regulate gene expression profiles. Studying the effects of chromatin structure alterations, which are caused by the addition/removal of functional groups to specific histone residues, are of great interest as a promising way to identify markers for cancer diagnosis, classify the disease and determine its prognosis, and these markers could be potential targets for the treatment of this disease in its different forms. This manuscript presents the current point of view regarding members of the recently described family of proteins that exhibit histone demethylase activity; histone demethylases are genetic regulators that play a fundamental role in both the activation and repression of genes and whose expression has been observed to increase in many types of cancer. Some fundamental aspects of their association with the development of cancer and their relevance as potential targets for the development of new therapeutic strategies at the epigenetic level are discussed in the following manuscript.

Hairless regulates heterochromatin maintenance and muscle stem cell function as a histone demethylase antagonist

2021 ◽  
Vol 118 (37) ◽  
pp. e2025281118
Author(s):  
Ling Liu ◽  
Cristina Rodriguez-Mateo ◽  
Polly Huang ◽  
Albin Huang ◽  
Alexander Lieu ◽  
...  
Keyword(s):  
Cell Function ◽  
Expression Profiles ◽  
Gene Expression Profiles ◽  
Genotoxic Stress ◽  
Histone Demethylases ◽  
Muscle Stem Cell ◽  
Muscle Stem Cells ◽  
Histone 3 ◽  
Age Related ◽  
Regenerative Ability

Skeletal muscle possesses remarkable regenerative ability because of the resident muscle stem cells (MuSCs). A prominent feature of quiescent MuSCs is a high content of heterochromatin. However, little is known about the mechanisms by which heterochromatin is maintained in MuSCs. By comparing gene-expression profiles from quiescent and activated MuSCs, we found that the mammalian Hairless (Hr) gene is expressed in quiescent MuSCs and rapidly down-regulated upon MuSC activation. Using a mouse model in which Hr can be specifically ablated in MuSCs, we demonstrate that Hr expression is critical for MuSC function and muscle regeneration. In MuSCs, loss of Hr results in reduced trimethylated Histone 3 Lysine 9 (H3K9me3) levels, reduced heterochromatin, increased susceptibility to genotoxic stress, and the accumulation of DNA damage. Deletion of Hr leads to an acceleration of the age-related decline in MuSC numbers. We have also demonstrated that despite the fact that Hr is homologous to a family of histone demethylases and binds to di- and trimethylated H3K9, the expression of Hr does not lead to H3K9 demethylation. In contrast, we show that the expression of Hr leads to the inhibition of the H3K9 demethylase Jmjd1a and an increase in H3K9 methylation. Taking these data together, our study has established that Hr is a H3K9 demethylase antagonist specifically expressed in quiescent MuSCs.

scholarly journals Molecular Diversity of Intrinsically Photosensitive Ganglion Cells

2018 ◽  
Author(s):  
Daniel Berg ◽  
Katherine Kartheiser ◽  
Megan Leyrer ◽  
Alexandra Saali ◽  
David Berson
Keyword(s):  
Gene Expression ◽  
Adult Mouse ◽  
Molecular Level ◽  
Ganglion Cells ◽  
Expression Profiles ◽  
Expression Patterns ◽  
Gene Expression Profiles ◽  
Retinal Ganglion ◽  
Pupillary Light ◽  
Reporter Mice

AbstractIntrinsically photosensitive retinal ganglion cells (ipRGCs) are rare mammalian photoreceptors essential for non-image-forming vision functions, such as circadian photoentrainment and the pupillary light reflex. They comprise multiple subtypes distinguishable by morphology, physiology, projections, and levels of expression of melanopsin (Opn4), their photopigment. The molecular programs that differentiate ipRGCs from other ganglion cells and ipRGC subtypes from one another remain elusive. Here, we present comprehensive gene expression profiles of early postnatal and adult mouse ipRGCs purified from two lines of reporter mice marking different sets of ipRGC subtypes. We find dozens of novel genes highly enriched in ipRGCs. We reveal that Rasgrp1 and Tbx20 are selectively expressed in subsets of ipRGCs, though these molecularly defined groups imperfectly match established ipRGC subtypes. We demonstrate that the ipRGCs regulating circadian photoentrainment are unexpectedly diverse at the molecular level. Our findings reveal unexpected complexity in gene expression patterns across mammalian ipRGC subtypes.

scholarly journals Autonomic Nerves Regulate Gene Expression Profiles in The Developing Ductus Arteriosus

2021 ◽  
Vol 35 (S1) ◽  
Author(s):  
Sayuki Oka ◽  
Hiroyuki Kuroda ◽  
Shota Tanifuji ◽  
Tatsunori Seki ◽  
Utako Yokoyama
Keyword(s):  
Gene Expression ◽  
Expression Profiles ◽  
Ductus Arteriosus ◽  
Gene Expression Profiles ◽  
Autonomic Nerves ◽  
Regulate Gene Expression ◽  
Regulate Gene

scholarly journals Transcriptional and Biochemical Effects of Cadmium and Manganese on the Defense System ofOctopus vulgarisParalarvae

2015 ◽  
Vol 2015 ◽  
pp. 1-11 ◽  
Author(s):  
Aldo Nicosia ◽  
Monica Salamone ◽  
Salvatore Mazzola ◽  
Angela Cuttitta
Keyword(s):  
Coastal Waters ◽  
Molecular Level ◽  
Anthropogenic Activities ◽  
Expression Profiles ◽  
Gene Expression Profiles ◽  
Octopus Vulgaris ◽  
Defense System ◽  
Biochemical Effects ◽  
Metabolic Functions ◽  
Dependent Inhibition

Due to anthropogenic activities the relative concentrations of cadmium and manganese have increased in the marine environment. Cephalopods are able to accumulate such metals and, as inhabitant of coastal waters,Octopus vulgarisis continuously exposed to anthropogenic activities. Since no study is available on the effects of heavy metals at molecular level in developing octopuses, herein we exposed 1-day-old paralarvae for 24 h to 10, 100, and 1000 μg/L of CdCl2or MnCl2. Cd exerted a concentration-dependent inhibition of survival and a reduction in growth rate was shown while Mn exposure did not affect the survival rate even at the highest concentrations. Gene expression profiles ofhsp70, sod, cat, andgstgenes were analyzed by quantitative real-time PCR and defined patterns of transcription were observed. Moreover posttranscriptional analyses were also performed suggesting the impairment of metabolic functions, under strong oxidative conditions (as occurred in paralarvae exposed to Cd) or the complete detoxification events (as occurred in paralarvae exposed to Mn).

scholarly journals Transcriptome Analysis of Gene Expression Profiles of Tomato Yellow Leaf Curl Virus-Infected Whiteflies over Different Viral Acquisition Access Periods

Insects ◽  
2020 ◽  
Vol 11 (5) ◽  
pp. 297 ◽  
Author(s):  
Meng Li ◽  
Jing Zhao ◽  
Yun-Lin Su
Keyword(s):  
Transcriptome Analysis ◽  
Molecular Level ◽  
Expression Profiles ◽  
Gene Expression Profiles ◽  
Tomato Yellow Leaf ◽  
Yellow Leaf ◽  
Transcriptional Responses ◽  
Tomato Production ◽  
Leaf Curl Virus ◽  
Leaf Curl

Tomato yellow leaf curl virus (TYLCV), which is transmitted by Bemisia tabaci in a persistent-circulative manner, threatens tomato production worldwide. Little is known about the complicated interaction during this process at the molecular level. In this study, viral AAPs at 0 h, 2 h, 6 h, 12 h and 48 h were investigated using a comparative transcriptome analysis to uncover the transcriptional responses of whiteflies to virus infection. Our results have shown that 755, 587, 1140 and 1347 differentially expressed genes (DEGs) were identified in the comparisons of the data of 0 h vs. 2 h, 0 h vs. 6 h, 0 h vs. 12 h and 0 h vs. 48 h, respectively. KEGG analysis showed that DEGs associated with metabolisms and signal transduction were down-regulated in virus-infected whiteflies. Additionally, 16 up-regulated putative transporter genes and 10 down-regulated genes associated with IL-17 signaling pathway were identified by time-associated gene cluster analysis. These data boost our comprehensions on whitefly-TYLCV interactions associated with different viral AAPs.

scholarly journals Comparative brain transcriptomic analyses of scouting across distinct behavioural and ecological contexts in honeybees

2014 ◽  
Vol 281 (1797) ◽  
pp. 20141868 ◽  
Author(s):  
Zhengzheng S. Liang ◽  
Heather R. Mattila ◽  
Sandra L. Rodriguez-Zas ◽  
Bruce R. Southey ◽  
Thomas D. Seeley ◽  
...  
Keyword(s):  
Gene Expression ◽  
Cross Validation ◽  
Nest Site ◽  
Molecular Level ◽  
Expression Profiles ◽  
Gene Expression Profiles ◽  
Molecular Signature ◽  
Class Prediction ◽  
Brain Gene Expression ◽  
Leave One Out

Individual differences in behaviour are often consistent across time and contexts, but it is not clear whether such consistency is reflected at the molecular level. We explored this issue by studying scouting in honeybees in two different behavioural and ecological contexts: finding new sources of floral food resources and finding a new nest site. Brain gene expression profiles in food-source and nest-site scouts showed a significant overlap, despite large expression differences associated with the two different contexts. Class prediction and ‘leave-one-out’ cross-validation analyses revealed that a bee's role as a scout in either context could be predicted with 92.5% success using 89 genes at minimum. We also found that genes related to four neurotransmitter systems were part of a shared brain molecular signature in both types of scouts, and the two types of scouts were more similar for genes related to glutamate and GABA than catecholamine or acetylcholine signalling. These results indicate that consistent behavioural tendencies across different ecological contexts involve a mixture of similarities and differences in brain gene expression.

scholarly journals Investigations on the oxygen dependence of a 2-oxoglutarate histone demethylase

2012 ◽  
Vol 449 (2) ◽  
pp. 491-496 ◽  
Author(s):  
Elena M. Sánchez-Fernández ◽  
Hanna Tarhonskaya ◽  
Khalid Al-Qahtani ◽  
Richard J. Hopkinson ◽  
James S. O. McCullagh ◽  
...  
Keyword(s):  
Steady State ◽  
Methylation Status ◽  
Kinetic Studies ◽  
Histone Demethylase ◽  
Histone Demethylases ◽  
Graded Response ◽  
Histone Lysine Demethylase ◽  
Demethylase Activity ◽  
Lysine Demethylase ◽  
Relevant Range

Histone Nϵ-methyl lysine demethylases are important in epigenetic regulation. KDM4E (histone lysine demethylase 4E) is a representative member of the large Fe(II)/2-oxoglutarate- dependent family of human histone demethylases. In the present study we report kinetic studies on the reaction of KDM4E with O2. Steady-state assays showed that KDM4E has a graded response to O2 over a physiologically relevant range of O2 concentrations. Pre-steady state assays implied that KDM4E reacts slowly with O2 and that there are variations in the reaction kinetics which are dependent on the methylation status of the substrate. The results demonstrate the potential for histone demethylase activity to be regulated by oxygen availability.

Agronomic and molecular analysis of heterosis in alfalfa

2011 ◽  
Vol 9 (2) ◽  
pp. 288-290 ◽  
Author(s):  
C. Scotti ◽  
M. Carelli ◽  
O. Calderini ◽  
F. Panara ◽  
P. Gaudenzi ◽  
...  
Keyword(s):  
Gene Expression ◽  
Dry Matter ◽  
Molecular Level ◽  
Expression Profiles ◽  
Gene Expression Profiles ◽  
Gene Ontology Analysis ◽  
Simple Sequence Repeat Markers ◽  
Genetic Information Processing ◽  
Parental Lines ◽  
Simple Sequence

Double ‘free-hybrids’ (DH) in alfalfa were obtained by crossing in a diallelic scheme, six multiplied simple hybrids (SH) derived from four partly inbred (S2) lines. Analysis of the specific combining ability demonstrated that the main source of variation was for dry matter yield (DMY) in DHs and supported heterosis values of DHs versus the best parent of an average +45% (ranging from +5 to +76%). Investigation at the molecular level was carried out by analysis of simple sequence repeat markers on the six parental SHs and 15 DH progenies and by comparison of gene expression profiles using microarrays of a single DH line to its parental lines. The variation of heterozygosity estimates of the DHs explained a small part (about 20%) of their variation in DMY, while the number of alleles was significantly related to DM performance (r = 0.61; P < 0.05). The microarray analysis identified genes with both significant additive and non-additive levels of expression in the hybrid compared with the parents. The majority of the variation in gene expression was additive (87%), but among the genes with a non-additive pattern of expression, the greater proportion of probe sets (86%) fell outside the parental range. Gene ontology analysis of these genes revealed the presence of a number of terms related to metabolism and genetic information processing.

scholarly journals Advances in Histone Demethylase KDM3A as a Cancer Therapeutic Target

Cancers ◽  
2020 ◽  
Vol 12 (5) ◽  
pp. 1098 ◽  
Author(s):  
Jung Yoo ◽  
Yu Hyun Jeon ◽  
Ha Young Cho ◽  
Sang Wu Lee ◽  
Go Woon Kim ◽  
...  
Keyword(s):  
Therapeutic Target ◽  
Structural Information ◽  
Therapeutic Agents ◽  
Histone Demethylase ◽  
Histone Demethylases ◽  
Selective Inhibitors ◽  
Lxxll Motif ◽  
Demethylase Activity ◽  
Potential Cancer ◽  
Insight Into

Lysine-specific histone demethylase 3 (KDM3) subfamily proteins are H3K9me2/me1 histone demethylases that promote gene expression. The KDM3 subfamily primarily consists of four proteins (KDM3A−D). All four proteins contain the catalytic Jumonji C domain (JmjC) at their C-termini, but whether KDM3C has demethylase activity is under debate. In addition, KDM3 proteins contain a zinc-finger domain for DNA binding and an LXXLL motif for interacting with nuclear receptors. Of the KDM3 proteins, KDM3A is especially deregulated or overexpressed in multiple cancers, making it a potential cancer therapeutic target. However, no KDM3A-selective inhibitors have been identified to date because of the lack of structural information. Uncovering the distinct physiological and pathological functions of KDM3A and their structure will give insight into the development of novel selective inhibitors. In this review, we focus on recent studies highlighting the oncogenic functions of KDM3A in cancer. We also discuss existing KDM3A-related inhibitors and review their potential as therapeutic agents for overcoming cancer.

Automated Tissue Analysis – a Bioinformatics Perspective

2005 ◽  
Vol 44 (01) ◽  
pp. 32-37 ◽  
Author(s):  
K. Boyce ◽  
A. Kriete
Keyword(s):  
Gene Expression ◽  
Machine Vision ◽  
Tissue Injury ◽  
Expression Profiles ◽  
Gene Expression Profiles ◽  
Quantitative Information ◽  
Point Of View ◽  
Data Sets ◽  
Tissue Analysis

Summary Objectives: Recent progress in automated tissue analysis (tissomics) provides reproducible phenotypical characterization of histological specimens. We introduce informatics tools to cluster and correlate quantitative tissue profiles with gene expression data. The great potential of synergies between tissue analysis and bioinformatics and its perspectives in medical research and computational diagnostics are discussed. Methods: Key enablers in microscopic imaging and machine vision are reviewed to perform a high-throughput tissue analysis. Methodologies are described and results are demonstrated that support a combined analysis of tissue with gene expression profiles whereby the consideration of individual responses is key. Results: Comprehensive histomorphometric profiles, extracted using machine vision, provide information regarding the components and heterogeneity of a tissue in a reproducible format amenable to data mining and analysis. Tissue quantitative information can be placed in synergetic context with bioinformatics data, such as gene expression profiles, for a more comprehensive stratification of individual responses. From a bioinformatics point of view tissue data are co-variants that support the identification of candidate genes relevant in tissue injury or disease. Conclusions: Progress in automated analytics enables the generation of quantitative data about tissue previously limited to visual histopathology. Such reproducible data sets can be statistically correlated and clustered throughout the continuum of bioinformatics. The combined approach supports a system-wide view of biology and has a potential to accelerate developments for a personalized computational diagnosis.

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