COMPUTATION BY ANNOTATION: MODELLING EPIGENETIC REGULATION

2008 ◽  
Vol 19 (05) ◽  
pp. 1087-1098
Author(s):  
FRANZISKA BIEGLER ◽  
MARK DALEY ◽  
M. ELIZABETH O. LOCKE
Keyword(s):  
Histone Modification ◽  
Epigenetic Regulation ◽  
Formal Model ◽  
Gene Annotation ◽  
Formal System ◽  
Regular Languages ◽  
Generative Capacity ◽  
Epigenetic Process

We present a formal model inspired by the epigenetic process of gene annotation via histone modification. In particular, we study the generative capacity of a system in which annotations on a set of strings control which substrings are ultimately produced by the system and in which only the annotations, and not the strings themselves, may be rewritten. On a biological level this represents a first attempt to better understand the computational limits of this form of epigenetic regulation. We introduce two different derivation modes for our formal system and show that these systems are actually quite weak. The weaker of the derivation modes is directly capable only of generating a subset of the regular languages while the more powerful derivation mode is also only capable of generating all regular languages modulo a begin- and an end-marker.

scholarly journals Bmi1 Augments Proliferation and Survival of Cortical Bone-Derived Stem Cells after Injury through Novel Epigenetic Signaling via Histone 3 Regulation

2021 ◽  
Vol 22 (15) ◽  
pp. 7813
Author(s):  
Lindsay Kraus ◽  
Chris Bryan ◽  
Marcus Wagner ◽  
Tabito Kino ◽  
Melissa Gunchenko ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Stem Cells ◽  
Dna Damage ◽  
Stem Cell ◽  
Histone Modification ◽  
Epigenetic Regulation ◽  
Critical Role ◽  
Proliferative Potential ◽  
Therapeutic Effects ◽  
Histone 3

Ischemic heart disease can lead to myocardial infarction (MI), a major cause of morbidity and mortality worldwide. Multiple stem cell types have been safely transferred into failing human hearts, but the overall clinical cardiovascular benefits have been modest. Therefore, there is a dire need to understand the basic biology of stem cells to enhance therapeutic effects. Bmi1 is part of the polycomb repressive complex 1 (PRC1) that is involved in different processes including proliferation, survival and differentiation of stem cells. We isolated cortical bones stem cells (CBSCs) from bone stroma, and they express significantly high levels of Bmi1 compared to mesenchymal stem cells (MSCs) and cardiac-derived stem cells (CDCs). Using lentiviral transduction, Bmi1 was knocked down in the CBSCs to determine the effect of loss of Bmi1 on proliferation and survival potential with or without Bmi1 in CBSCs. Our data show that with the loss of Bmi1, there is a decrease in CBSC ability to proliferate and survive during stress. This loss of functionality is attributed to changes in histone modification, specifically histone 3 lysine 27 (H3K27). Without the proper epigenetic regulation, due to the loss of the polycomb protein in CBSCs, there is a significant decrease in cell cycle proteins, including Cyclin B, E2F, and WEE as well as an increase in DNA damage genes, including ataxia-telangiectasia mutated (ATM) and ATM and Rad3-related (ATR). In conclusion, in the absence of Bmi1, CBSCs lose their proliferative potential, have increased DNA damage and apoptosis, and more cell cycle arrest due to changes in epigenetic modifications. Consequently, Bmi1 plays a critical role in stem cell proliferation and survival through cell cycle regulation, specifically in the CBSCs. This regulation is associated with the histone modification and regulation of Bmi1, therefore indicating a novel mechanism of Bmi1 and the epigenetic regulation of stem cells.

scholarly journals Broad genic repression domains signify enhanced silencing of oncogenes

2020 ◽  
Vol 11 (1) ◽  
Author(s):  
Dongyu Zhao ◽  
Lili Zhang ◽  
Min Zhang ◽  
Bo Xia ◽  
Jie Lv ◽  
...  
Keyword(s):  
Histone Modification ◽  
Epigenetic Regulation ◽  
Normal Cell ◽  
Cell Types ◽  
Regulatory Elements ◽  
Integrative Analysis ◽  
Epigenetic Alterations ◽  
Gain Of Function ◽  
Repressive Histone Modification ◽  
Cancer Phenotypes

Abstract Cancers result from a set of genetic and epigenetic alterations. Most known oncogenes were identified by gain-of-function mutations in cancer, yet little is known about their epigenetic features. Through integrative analysis of 11,596 epigenomic profiles and mutations from >8200 tumor-normal pairs, we discover broad genic repression domains (BGRD) on chromatin as an epigenetic signature for oncogenes. A BGRD is a widespread enrichment domain of the repressive histone modification H3K27me3 and is further enriched with multiple other repressive marks including H3K9me3, H3K9me2, and H3K27me2. Further, BGRD displays widespread enrichment of repressed cis-regulatory elements. Shortening of BGRDs is linked to derepression of transcription. BGRDs at oncogenes tend to be conserved across normal cell types. Putative tumor-promoting genes and lncRNAs defined using BGRDs are experimentally verified as required for cancer phenotypes. Therefore, BGRDs play key roles in epigenetic regulation of cancer and provide a direction for mutation-independent discovery of oncogenes.

scholarly journals Accelerating the field of epigenetic histone modification through mass spectrometry-based approaches

2020 ◽  
pp. mcp.R120.002257
Author(s):  
Congcong Lu ◽  
Mariel Coradin ◽  
Elizabeth G Porter ◽  
Benjamin A Garcia
Keyword(s):  
Mass Spectrometry ◽  
Molecular Biology ◽  
Histone Modification ◽  
High Throughput ◽  
Epigenetic Regulation ◽  
Associated Factors ◽  
Chemical Biology ◽  
Post Translational Modifications ◽  
Histone Ptms ◽  
Chromatin Biology

Histone post-translational modifications (PTMs) are one of the main mechanisms of epigenetic regulation. Dysregulation of histone PTMs leads to many human diseases, such as cancer. Due to its high-throughput, accuracy, and flexibility, mass spectrometry (MS) has emerged as a powerful tool in the epigenetic histone modification field, allowing the comprehensive and unbiased analysis of histone PTMs and chromatin-associated factors. Coupled with various techniques from molecular biology, biochemistry, chemical biology and biophysics, MS has been employed to characterize distinct aspects of histone PTMs in the epigenetic regulation of chromatin functions. In this review we will describe advancements in the field of MS that have facilitated the analysis of histone PTMs and chromatin biology.  

GENERATIVE CAPACITY OF SUBREGULARLY TREE CONTROLLED GRAMMARS

2010 ◽  
Vol 21 (05) ◽  
pp. 723-740 ◽  
Author(s):  
JÜRGEN DASSOW ◽  
RALF STIEBE ◽  
BIANCA TRUTHE
Keyword(s):  
Regular Language ◽  
Regular Languages ◽  
Derivation Tree ◽  
Generative Capacity ◽  
The Family ◽  
Context Free ◽  
Context Free Grammars

Tree controlled grammars are context-free grammars where the associated language only contains those terminal words which have a derivation where the word of any level of the corresponding derivation tree belongs to a given regular language. We present some results on the power of such grammars where we restrict the regular languages to some known subclasses of the family of regular languages.

scholarly journals Coordinated Epigenetic Regulation in Plants: A Potent Managerial Tool to Conquer Biotic Stress

2022 ◽  
Vol 12 ◽  
Author(s):  
Chien-Yu Huang ◽  
Hailing Jin
Keyword(s):  
Gene Expression ◽  
Dna Methylation ◽  
Histone Modification ◽  
Epigenetic Regulation ◽  
Biotic Stress ◽  
Environmental Changes ◽  
Crop Protection ◽  
Fine Tuning ◽  
Transcriptional Level ◽  
Microbial Infection

Plants have evolved variable phenotypic plasticity to counteract different pathogens and pests during immobile life. Microbial infection invokes multiple layers of host immune responses, and plant gene expression is swiftly and precisely reprogramed at both the transcriptional level and post-transcriptional level. Recently, the importance of epigenetic regulation in response to biotic stresses has been recognized. Changes in DNA methylation, histone modification, and chromatin structures have been observed after microbial infection. In addition, epigenetic modifications may be preserved as transgenerational memories to allow the progeny to better adapt to similar environments. Epigenetic regulation involves various regulatory components, including non-coding small RNAs, DNA methylation, histone modification, and chromatin remodelers. The crosstalk between these components allows precise fine-tuning of gene expression, giving plants the capability to fight infections and tolerant drastic environmental changes in nature. Fully unraveling epigenetic regulatory mechanisms could aid in the development of more efficient and eco-friendly strategies for crop protection in agricultural systems. In this review, we discuss the recent advances on the roles of epigenetic regulation in plant biotic stress responses.

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