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 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.
Highlights
It is becoming increasingly apparent that DNA sequences alone do not dictate gene activity or disease risk
Half of the females produced by this cross are a Pgrwt/Cre, Ezh2flox/flox expressing cre recombinase and with both Enhancer of zeste homolog 2 (EZH2) alleles floxed (Ezh2cKO)
This study suggested that EZH2 could be a therapeutic target for treating recurrent miscarriage
Summary
It is becoming increasingly apparent that DNA sequences alone do not dictate gene activity or disease risk. Cytosine methylation generally results in transcriptional repression, as these biomolecular changes may interfere with transcription factors binding and activating their promoter sites. This mechanism promotes silencing by regulating tissue-specific gene expression, X chromosome inactivation, and genomic imprinting [5]. We will focus on histone protein methylation as one way EZH2, the epigenetic modifier being considered, acts to induce such modification. In contrast to typically suppressive effects of DNA methylation, the net result of histone methylation on gene expression is variable depending on the specific histone protein and amino acid residue modified. Histone modifications interact with each other and with DNA methylation [13] Enzymes that catalyze these fundamental epigenetic alterations are identified as “writers” and “erasers” [14]. We will consider the role of EZH2 in uterine diseases
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