Epigenetic function in neurodevelopment and cognitive impairment

Neuroforum ◽  
2021 ◽  
Vol 0 (0) ◽  
Author(s):  
Mira Jakovcevski ◽  
Geraldine Zimmer-Bensch
Keyword(s):  
Brain Development ◽  
Neuronal Migration ◽  
Treatment Options ◽  
Regulation Of Gene Expression ◽  
Noncoding Rnas ◽  
Molecular Processes ◽  
High Prevalence ◽  
Genes Encoding ◽  
Epigenetic Regulators ◽  
Epigenetic Processes

Abstract Brain development comprises a fine-tuned ensemble of molecular processes that need to be orchestrated in a very coordinated way throughout time and space. A wide array of epigenetic mechanisms, ranging from DNA methylation and histone modifications to noncoding RNAs, have been identified for their major role in guiding developmental processes such as progenitor proliferation, neuronal migration, and differentiation through precise regulation of gene expression programs. The importance of epigenetic processes during development is reflected by the high prevalence of neurodevelopmental diseases which are caused by a lack or mutation of genes encoding for transcription factors and other epigenetic regulators. Most of these factors process central functions for proper brain development, and respective mutations lead to severe cognitive defects. A better understanding of epigenetic programs during development might open new routes toward better treatment options for related diseases.

scholarly journals Expression levels of long noncoding natural antisense transcripts overlapping the UGT73C6 gene affect rosette size of Arabidopsis thaliana

2021 ◽  
Author(s):  
Shiv Kumar Meena ◽  
Michel Heidecker ◽  
Susanne Engelmann ◽  
Ammar Jaber ◽  
Tebbe de Vries ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Arabidopsis Thaliana ◽  
Leaf Growth ◽  
Regulation Of Gene Expression ◽  
Noncoding Rnas ◽  
Leaf Size ◽  
Expression Levels ◽  
Genes Encoding ◽  
Constitutive Overexpression ◽  
Gene Overlapping

SummaryNatural antisense long noncoding RNAs (lncNATs) are involved in the regulation of gene expression in plants, modulating different relevant developmental processes and responses to various stimuli. We identified and characterized two lncNATs (NAT1UGT73C6 and NAT2UGT73C6, collectively NATsUGT73C6) in Arabidopsis thaliana that are transcribed from a gene overlapping UGT73C6, a member of the UGT73C subfamily of genes encoding UDP-glycosyltransferases (UGTs). Expression of both NATsUGT73C6 is developmentally controlled and occurs independently of the transcription of UGT73C6 in cis. Downregulation of NATsUGT73C6 levels through artificial microRNAs results in a reduction of the rosette area, while constitutive overexpression of NAT1UGT73C6 or NAT2UGT73C6 leads to the opposite phenotype, an increase in rosette size. This activity of NATsUGT73C6 relies on its RNA sequence, and, although modulation of UGT73C6 in cis cannot be excluded, the observed phenotypes are not a consequence of the regulation of UGT73C6 in trans. The NATsUGT73C6 levels were shown to affect cell proliferation and thus individual leaf size. Consistent with this concept, our data suggest that the NATsUGT73C6 modulate the expression levels of key transcription factors involved in regulating leaf growth by modulating cell proliferation. These findings thus reveal an additional regulatory layer on the process of leaf growth.

Lighting a path: genetic studies pinpoint neurodevelopmental mechanisms in autism and related disorders

2012 ◽  
Vol 14 (3) ◽  
pp. 239-252
Keyword(s):  
Molecular Mechanisms ◽  
Protein Localization ◽  
Regulation Of Gene Expression ◽  
Neuronal Cell ◽  
Mrna Splicing ◽  
Genetic Mutations ◽  
Scaffolding Proteins ◽  
Molecular Processes ◽  
Genetic Studies ◽  
Novel Treatments

In this review, we outline critical molecular processes that have been implicated by discovery of genetic mutations in autism. These mechanisms need to be mapped onto the neurodevelopment step(s) gone awry that may be associated with cause in autism. Molecular mechanisms include: (i) regulation of gene expression; (ii) pre-mRNA splicing; (iii) protein localization, translation, and turnover; (iv) synaptic transmission; (v) cell signaling; (vi) the functions of cytoskeletal and scaffolding proteins; and (vii) the function of neuronal cell adhesion molecules. While the molecular mechanisms appear broad, they may converge on only one of a few steps during neurodevelopment that perturbs the structure, function, and/or plasticity of neuronal circuitry. While there are many genetic mutations involved, novel treatments may need to target only one of few developmental mechanisms.

scholarly journals Neglected femoral neck fractures in cerebral palsy: a narrative review

2020 ◽  
Vol 5 (1) ◽  
pp. 58-64
Author(s):  
Giuseppe Toro ◽  
Antimo Moretti ◽  
Marco Paoletta ◽  
Annalisa De Cicco ◽  
Adriano Braile ◽  
...  
Keyword(s):  
Cerebral Palsy ◽  
Femoral Neck ◽  
Motor Function ◽  
Treatment Options ◽  
High Morbidity ◽  
Fibular Graft ◽  
Motor Impairments ◽  
High Prevalence ◽  
Neck Fracture

Hip fractures are severe conditions with a high morbidity and mortality, especially when the diagnosis is delayed, and if formulated over 30 days after the injury, is termed a ‘neglected femoral neck fracture’ (NFNF). Cerebral palsy (CP) is probably one of the major risk factors for NFNF in Western countries, mainly because of both cognitive and motor impairments. However, considering the high prevalence of fractures in these patients, the incidence of NFNF in this population is probably underestimated, and this condition might result in persistent hip or abdominal pain. Several techniques are available for the treatment of NFNF (i.e. muscle pedicle bone graft, fixation with fibular graft, valgisation osteotomy), but most of them could affect motor function. Motor function must be preserved for as long as possible, in order to enhance the quality of life of CP patients. After discussing published NFNF cases in CP patients and available treatment options, a practical approach is proposed to facilitate the orthopaedic surgeon to both early identify and appropriately manage these challenging fractures. Cite this article: EFORT Open Rev 2020;5:58-64. DOI: 10.1302/2058-5241.5.190019

scholarly journals Involvement of Thyroid Hormones in Brain Development and Cancer

Cancers ◽  
2021 ◽  
Vol 13 (11) ◽  
pp. 2693
Author(s):  
Gabriella Schiera ◽  
Carlo Maria Di Liegro ◽  
Italia Di Liegro
Keyword(s):  
Nervous System ◽  
Thyroid Hormones ◽  
Brain Development ◽  
Placental Transfer ◽  
Regulation Of Gene Expression ◽  
Mammalian Brain ◽  
Cancer Proliferation ◽  
Fetal Thyroid ◽  
Genomic Effects ◽  
And Function

The development and maturation of the mammalian brain are regulated by thyroid hormones (THs). Both hypothyroidism and hyperthyroidism cause serious anomalies in the organization and function of the nervous system. Most importantly, brain development is sensitive to TH supply well before the onset of the fetal thyroid function, and thus depends on the trans-placental transfer of maternal THs during pregnancy. Although the mechanism of action of THs mainly involves direct regulation of gene expression (genomic effects), mediated by nuclear receptors (THRs), it is now clear that THs can elicit cell responses also by binding to plasma membrane sites (non-genomic effects). Genomic and non-genomic effects of THs cooperate in modeling chromatin organization and function, thus controlling proliferation, maturation, and metabolism of the nervous system. However, the complex interplay of THs with their targets has also been suggested to impact cancer proliferation as well as metastatic processes. Herein, after discussing the general mechanisms of action of THs and their physiological effects on the nervous system, we will summarize a collection of data showing that thyroid hormone levels might influence cancer proliferation and invasion.

scholarly journals ARID2 Chromatin Remodeler in Hepatocellular Carcinoma

Cells ◽  
2020 ◽  
Vol 9 (10) ◽  
pp. 2152
Author(s):  
Robin Loesch ◽  
Linda Chenane ◽  
Sabine Colnot
Keyword(s):  
Gene Expression ◽  
Hepatocellular Carcinoma ◽  
Associated Factors ◽  
Regulation Of Gene Expression ◽  
Specific Gene ◽  
Chromatin Remodeler ◽  
Chromatin Remodelers ◽  
Genes Encoding ◽  
Gene Alterations

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.

scholarly journals Emerging roles for motor proteins in progenitor cell behavior and neuronal migration during brain development

Cytoskeleton ◽  
2016 ◽  
Vol 73 (9) ◽  
pp. Spc1-Spc1
Author(s):  
Tiago J. Dantas ◽  
Aurelie Carabalona ◽  
Daniel Jun-Kit Hu ◽  
Richard B. Vallee
Keyword(s):  
Brain Development ◽  
Neuronal Migration ◽  
Progenitor Cell ◽  
Motor Proteins ◽  
Cell Behavior

PREVALANCE OF HEAD AND NECK CANCER IN UPPER ASSAM: AN INSTITUTIONAL STUDY.

2021 ◽  
pp. 50-51
Author(s):  
Ayesha Agarwal ◽  
Trishan Paul ◽  
Rudra Kanta Gogoi ◽  
Rheetwik Baruah ◽  
Chiranjeev Baruah
Keyword(s):  
Oral Cavity ◽  
Head And Neck ◽  
Treatment Options ◽  
Population Based ◽  
Population Based Study ◽  
Medical College ◽  
Starting Point ◽  
High Prevalence ◽  
North Eastern ◽  
Total Body

In India, head and neck cancers (HNCA) account for 14.3% cancers at all sites. In North-eastern India, there is a high prevalence of HNCA which can be associated with pervasive habit of using tobacco, lime and betel. The alarmingly high prevalence of cancers of head and neck in this part of India has prompted us to take up this study. Ahospital-based study on prevalence of cancer in various head and neck regions like oropharynx, oral cavity, pharynx, larynx, salivary glands and nasal cavity was conducted in Department of Radiation Oncology, Assam Medical College and Hospital from June 2020 to May 2021.The prevalence is found to be signicantly high at 57.59%, affecting males more than females in the age group of 50-59 years. HNCA of hypopharynx and oral cavity constituted a major burden of total body cancer. This study hopes to quantify and analyse the HNCAspectrum and should help as a starting point for a much needed population based study in this region. Acomprehensive effort is required to identify the cause of such high prevalence of HNCAin this region of India, generate awareness and treatment options suited to meet this challenge.

scholarly journals MARVELD1 depletion leads to dysfunction of motor and cognition via regulating glia-dependent neuronal migration during brain development

2018 ◽  
Vol 9 (10) ◽  
Author(s):  
Weizhe Liu ◽  
Fang Han ◽  
Shuai Qu ◽  
Yuanfei Yao ◽  
Jianxiang Zhao ◽  
...  
Keyword(s):  
Brain Development ◽  
Neuronal Migration

scholarly journals Epigenomic regulation of heart failure: integrating histone marks, long noncoding RNAs, and chromatin architecture

F1000Research ◽  
2018 ◽  
Vol 7 ◽  
pp. 1713 ◽  
Author(s):  
Timothy A. McKinsey ◽  
Thomas M. Vondriska ◽  
Yibin Wang
Keyword(s):  
Heart Failure ◽  
Therapeutic Potential ◽  
Noncoding Rnas ◽  
Loss Of Function ◽  
Sequencing Technologies ◽  
Recent Developments ◽  
Non Coding Rnas ◽  
Epigenomic Regulation ◽  
Generation Sequencing ◽  
Epigenetic Processes

Epigenetic processes are known to have powerful roles in organ development across biology. It has recently been found that some of the chromatin modulatory machinery essential for proper development plays a previously unappreciated role in the pathogenesis of cardiac disease in adults. Investigations using genetic and pharmacologic gain- and loss-of-function approaches have interrogated the function of distinct epigenetic regulators, while the increased deployment of the suite of next-generation sequencing technologies have fundamentally altered our understanding of the genomic targets of these chromatin modifiers. Here, we review recent developments in basic and translational research that have provided tantalizing clues that may be used to unlock the therapeutic potential of the epigenome in heart failure. Additionally, we provide a hypothesis to explain how signal-induced crosstalk between histone tail modifications and long non-coding RNAs triggers chromatin architectural remodeling and culminates in cardiac hypertrophy and fibrosis.

scholarly journals Nitrous oxide production and consumption: regulation of gene expression by gas-sensitive transcription factors

2012 ◽  
Vol 367 (1593) ◽  
pp. 1213-1225 ◽  
Author(s):  
Stephen Spiro
Keyword(s):  
Nitrous Oxide ◽  
Transcription Initiation ◽  
Regulatory Networks ◽  
Regulation Of Gene Expression ◽  
Environmental Signals ◽  
Production And Consumption ◽  
Genes Encoding ◽  
Nitrous Oxide Production ◽  
Biochemical Mechanisms ◽  
Nitrate And Nitrite

Several biochemical mechanisms contribute to the biological generation of nitrous oxide (N 2 O). N 2 O generating enzymes include the respiratory nitric oxide (NO) reductase, an enzyme from the flavo-diiron family, and flavohaemoglobin. On the other hand, there is only one enzyme that is known to use N 2 O as a substrate, which is the respiratory N 2 O reductase typically found in bacteria capable of denitrification (the respiratory reduction of nitrate and nitrite to dinitrogen). This article will briefly review the properties of the enzymes that make and consume N 2 O, together with the accessory proteins that have roles in the assembly and maturation of those enzymes. The expression of the genes encoding the enzymes that produce and consume N 2 O is regulated by environmental signals (typically oxygen and NO) acting through regulatory proteins, which, either directly or indirectly, control the frequency of transcription initiation. The roles and mechanisms of these proteins, and the structures of the regulatory networks in which they participate will also be reviewed.

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