Histone Demethylases

A topical collection in Epigenomes (ISSN 2075-4655).

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Editor


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Collection Editor
Department of Radiation Oncology, UAB Comprehensive Cancer Center, Birmingham, AL 35249, USA
Interests: p53; apoptosis; cancer therapy; cancer biology; cancer cell biology; tumor biology; DNA damage; molecular oncology; clinical oncology; medical oncology

Topical Collection Information

Dear Colleagues,

Histone demethylases are an expanding group of epigenetic regulators of chromatin structure and gene expression and play diverse roles in both embryonal development and disease. These histone demethylating enzymes antagonize the activity of histone methyl transferases by removing methyl groups from the specific lysine residue in the histones and in other non-histone target proteins, such as p53.

The first histone demethylase to be discovered was LSD1 (KDM1), an enzyme of critical importance for embryogenesis and embryonic stem cells. Recent evidence indicates that histone demethylases play important roles in tumorigenesis, epithelial-to-mesenchymal transition, invasion, metastases, and cancer stem cell phenotypes. For instance, Jumonji family histone demethylases collaborate with pathogenic H3K27M mutations in pediatric diffuse intrinsic pontine gliomas by removing the tri-methylation mark from histone H3 lysine 27, thus triggering global de-repression of genes involved in cancer stemness. Accordingly, overexpression of Jumonji family demethylases has been linked to chemotherapy and radiation resistance, and poor prognosis. Emerging are the functions of histone demethylases in neurodegenerative diseases, such as Alzheimer’s and Parkinson’s diseases.  

The aim of this Topical Collection is to highlight the diverse roles histone demethylases play in embryonic development and human diseases, such as cancer and neurodegenerative disease. We are particularly interested in experimental basic science and translational research studies focusing on pharmacological targeting histone demethylases, as well as review articles that would illuminate recent advances in our understanding of histone demethylase functions in cancer and other diseases.

Dr. Anatoly Nikolaev
Collection Editor

Manuscript Submission Information

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Keywords

  • histones
  • H3K27
  • H3K27M
  • methylation
  • demethylation
  • Jumonji
  • LSD1
  • KDM1
  • embryogenesis
  • KDM5
  • KDM6
  • cancer stem cells
  • pediatric glioma
  • leukemia
  • lymphoma
  • multiple myeloma
  • neurodegeneration
  • Alzheimer’s disease
  • Parkinson’s diseases

Published Papers (1 paper)

2020

13 pages, 1710 KiB  
Review
The Roles of the Histone Protein Modifier EZH2 in the Uterus and Placenta
by Ana M. Mesa, Cheryl S. Rosenfeld, Geetu Tuteja, Theresa I. Medrano and Paul S. Cooke
Epigenomes 2020, 4(3), 20; https://doi.org/10.3390/epigenomes4030020 - 02 Sep 2020
Cited by 7 | Viewed by 4973
Abstract
Epigenetic modifications regulate normal physiological, as well as pathological processes in various organs, including the uterus and placenta. Both organs undergo dramatic and rapid restructuring that depends upon precise orchestration of events. Epigenetic changes that alter transcription and translation of gene-sets regulate such [...] Read more.
Epigenetic modifications regulate normal physiological, as well as pathological processes in various organs, including the uterus and placenta. Both organs undergo dramatic and rapid restructuring that depends upon precise orchestration of events. Epigenetic changes that alter transcription and translation of gene-sets regulate such responses. Histone modifications alter the chromatin structure, thereby affecting transcription factor access to gene promoter regions. Binding of histones to DNA is regulated by addition or removal of subunit methyl and other groups, which can inhibit or stimulate transcription. Enhancer of zeste homolog 2 (EZH2) is the catalytic subunit of polycomb repressive complex 2 (PRC2) that catalyzes tri-methylation of histone H3 at Lys 27 (H3K27me3) and subsequently suppresses transcription of genes bound by such histones. Uterine EZH2 expression exerts a critical role in development and function of this organ with deletion of this gene resulting in uterine hyperplasia and expression of cancer-associated transcripts. Elucidating the roles of EZH2 in uterus and placenta is essential as EZH2 dysregulation is associated with several uterine and placental pathologies. Herein, we discuss EZH2 functions in uterus and placenta, emphasizing its physiological and pathological importance. Full article
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