Mutation spectra of histone methyltransferases with canonical SET domains and EZH2-targeted therapy

Epigenomics ◽  
2016 ◽  
Vol 8 (2) ◽  
pp. 285-305 ◽  
Author(s):  
Masaru Katoh
Keyword(s):  
Targeted Therapy ◽  
Histone Methyltransferases ◽  
Set Domains ◽  
Mutation Spectra

scholarly journals SET Domains of Histone Methyltransferases Recognize ISWI-Remodeled Nucleosomal Species

2009 ◽  
Vol 30 (3) ◽  
pp. 552-564 ◽  
Author(s):  
Wladyslaw A. Krajewski ◽  
Joseph C. Reese
Keyword(s):  
Gene Expression ◽  
Amino Acid ◽  
Chromatin Remodeling ◽  
Histone Methylation ◽  
Epigenetic Mechanism ◽  
Set Domain ◽  
Histone Methyltransferases ◽  
Core Histones ◽  
Weak Activity ◽  
Set Domains

ABSTRACT The trithorax (trxG) and Polycomb (PcG) group proteins recognize and propagate inheritable patterns of gene expression through a poorly understood epigenetic mechanism. A distinguishing feature of these proteins is the presence of a 130-amino-acid methyltransferase domain (SET), which catalyzes the methylation of histones. It is still not clear how SET proteins distinguish gene expression states, how they are targeted, or what regulates their substrate specificity. Many SET domain-containing proteins show robust activity on core histones but relatively weak activity on intact nucleosomes, their physiological substrate. Here, we examined the binding of two SET domain-containing proteins, ALL1 and SET7, to chromatin substrates. The SET domains from these proteins bind and methylate intact nucleosomes poorly but can recognize disrupted nucleosomal structures associated with transcribed chromatin. Interestingly, the remodeling of dinucleosomes by the ISWI class of ATP-dependent chromatin remodeling enzymes stimulated the binding of SET domains to chromatin and the methylation of H3 within the nucleosome. Unexpectedly, dinucleosomes remodeled by SWI/SNF were poor substrates. Thus, SET domains can distinguish nucleosomes altered by these two classes of remodeling enzymes. Our study reveals novel insights into the mechanism of how SET domains recognize different chromatin states and specify histone methylation at active loci.

How do histone modifications contribute to transgenerational epigenetic inheritance in C. elegans?

2020 ◽  
Vol 48 (3) ◽  
pp. 1019-1034 ◽  
Author(s):  
Rachel M. Woodhouse ◽  
Alyson Ashe
Keyword(s):  
Histone Modifications ◽  
Molecular Mechanisms ◽  
Epigenetic Inheritance ◽  
Nematode Caenorhabditis Elegans ◽  
Histone Methyltransferases ◽  
Transgenerational Epigenetic Inheritance ◽  
C Elegans ◽  
Recent Developments ◽  
Gene Regulatory

Gene regulatory information can be inherited between generations in a phenomenon termed transgenerational epigenetic inheritance (TEI). While examples of TEI in many animals accumulate, the nematode Caenorhabditis elegans has proven particularly useful in investigating the underlying molecular mechanisms of this phenomenon. In C. elegans and other animals, the modification of histone proteins has emerged as a potential carrier and effector of transgenerational epigenetic information. In this review, we explore the contribution of histone modifications to TEI in C. elegans. We describe the role of repressive histone marks, histone methyltransferases, and associated chromatin factors in heritable gene silencing, and discuss recent developments and unanswered questions in how these factors integrate with other known TEI mechanisms. We also review the transgenerational effects of the manipulation of histone modifications on germline health and longevity.

Lungenkarzinom: Genomisch stratefiziert behandeln: Wohin geht die Entwicklung?

2012 ◽  
Vol 03 (04) ◽  
pp. 184-185
Author(s):  
Christine Vetter
Keyword(s):  
Targeted Therapy

Die „Targeted Therapy” hat in den vergangenen Jahren in vielen Bereichen der Onkologie Fuß gefasst und gewinnt auch beim Lungenkarzinom zunehmend an Boden. Wie sich diese neue Therapierichtung künftig entwickeln kann, war eines der Themen beim diesjährigen Deutschen Krebskongress in Berlin.

Atopic dermatitis: new horizons of therapy

2019 ◽  
Vol 1 (7) ◽  
pp. 29-32 ◽  
Author(s):  
L. S. Kruglova ◽  
E. M. Gensler
Keyword(s):  
Blood Pressure ◽  
Immune Response ◽  
Allergic Rhinitis ◽  
Atopic Dermatitis ◽  
Targeted Therapy ◽  
Inflammatory Response ◽  
Bronchial Asthma ◽  
New Horizons ◽  
The Past

Over the past decades, the first breakthrough milestone in the treatment of severe forms of atopic dermatitis (AD) has been targeted therapy aimed at inhibiting IL-4 and IL-13. This was made possible thanks to advances in the understanding of the pathogenesis of AD, the driver of which is the Th2-type immune response, which also underlies such manifestations of atopy as bronchial asthma, allergic rhinitis, and polynosis. In the case of the Th2-type immune response, cytokines IL-4 and IL-13 are secreted, which are the main promoters of the inflammatory response in AD. Inhibition of IL-4 and IL-13 leads to the prevention of inflammation and is an effective approach to therapy. The use of therapy aimed at inhibition of cytokines allows you to effectively cope with the manifestations of severe and moderately severe blood pressure.

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