Contribution of the paternal histone epigenome to the preimplantation embryo.

The paternal germline contains a plethora of information that extends beyond DNA. Packaged within the sperm cell is a wealth of epigenetic information, including DNA methylation, small RNAs, and chromatin associated histone proteins and their covalently attached post-translational modifications. Paternal chromatin is particularly unique, as during the process of spermatogenesis, nearly all histones are evicted from the genome with only a small percentage retained in the mature sperm cell.

RNA modification to the rescue!

RNA expression of endogenous retroviral elements poses a threat to the genome and to cell function, which may ultimately result in disease. Recently published in Nature, Chelmicki and colleagues (2021) identify mA mRNA methylation as a form of regulation to defend the cell against these attacks.

Systematic genetic and proteomic screens during gametogenesis identify H2BK34 methylation as an evolutionary conserved meiotic mark.

Background: Gametes are highly differentiated cells specialized to carry and protect the parental genetic information. During male germ cell maturation, histone proteins undergo distinct changes that result in a highly compacted chromatin organization. Technical difficulties exclude comprehensive analysis of precise histone mutations during mammalian spermatogenesis.

Gcn5-Mediated Histone Acetylation Governs Nucleosome Dynamics in Spermiogenesis.

During mammalian spermatogenesis, germ cell chromatin undergoes dramatic histone acetylation-mediated reorganization, whereby 90%-99% of histones are evicted. Given the potential role of retained histones in fertility and embryonic development, the genomic location of retained nucleosomes is of great interest. However, the ultimate position and mechanisms underlying nucleosome eviction or retention are poorly understood, including several studies utilizing micrococcal-nuclease sequencing (MNase-seq) methodologies reporting remarkably dissimilar locations.

Histone Acetyltransferase p300 Induces De Novo Super-Enhancers to Drive Cellular Senescence.

Accumulation of senescent cells during aging contributes to chronic inflammation and age-related diseases. While senescence is associated with profound alterations of the epigenome, a systematic view of epigenetic factors in regulating senescence is lacking. Here, we curated a library of short hairpin RNAs for targeted silencing of all known epigenetic proteins and performed a high-throughput screen to identify key candidates whose downregulation can delay replicative senescence of primary human cells.

Histone modification signatures in human sperm distinguish clinical abnormalities.

Purpose: Alternations to the paternal epigenome, specifically the components of sperm chromatin, can lead to infertility in humans and potentially transmit aberrant information to the embryo. One key component of sperm chromatin is the post-translational modification of histones (PTMs). We previously identified a comprehensive profile of histone PTMs in normozoospermic sperm; however, only specific histone PTMs have been identified in abnormal sperm by antibody-based approaches and comprehensive changes to histone PTM profiles remain unknown.

Humanized H19/Igf2 locus reveals diverged imprinting mechanism between mouse and human and reflects Silver-Russell syndrome phenotypes.

Genomic imprinting affects a subset of genes in mammals, such that they are expressed in a monoallelic, parent-of-origin-specific manner. These genes are regulated by imprinting control regions (ICRs), cis-regulatory elements that exhibit allele-specific differential DNA methylation. Although genomic imprinting is conserved in mammals, ICRs are genetically divergent across species.

Comprehensive analysis of histone post-translational modifications in mouse and human male germ cells.

Background: During the process of spermatogenesis, male germ cells undergo dramatic chromatin reorganization, whereby most histones are replaced by protamines, as part of the pathway to compact the genome into the small nuclear volume of the sperm head. Remarkably, approximately 90 % (human) to 95 % (mouse) of histones are evicted during the process. An intriguing hypothesis is that post-translational modifications (PTMs) decorating histones play a critical role in epigenetic regulation of spermatogenesis and embryonic development following fertilization.

MicroRNA in Ovarian Biology and Disease.

MicroRNAs (miRNAs) are posttranscriptional gene regulatory molecules that show regulated expression within ovarian tissue. Most research investigating miRNAs in the ovary has relied exclusively on in vitro analyses. In this review, we highlight those few studies in which investigators have illustrated an in vivo effect of miRNAs on ovarian function.

Characterization of BRD4 during mammalian postmeiotic sperm development.

During spermiogenesis, the postmeiotic phase of mammalian spermatogenesis, transcription is progressively repressed as nuclei of haploid spermatids are compacted through a dramatic chromatin reorganization involving hyperacetylation and replacement of most histones with protamines. Although BRDT functions in transcription and histone removal in spermatids, it is unknown whether other BET family proteins play a role. Immunofluorescence of spermatogenic cells revealed BRD4 in a ring around the nuclei of spermatids containing hyperacetylated histones.

Developmental programming: gestational bisphenol-A treatment alters trajectory of fetal ovarian gene expression.

Bisphenol-A (BPA), a ubiquitous environmental endocrine disrupting chemical, is a component of polycarbonate plastic and epoxy resins. Because of its estrogenic properties, there is increasing concern relative to risks from exposures during critical periods of early organ differentiation. Prenatal BPA treatment in sheep results in low birth weight, hypergonadotropism, and ovarian cycle disruptions.

Developmental programming: gestational testosterone treatment alters fetal ovarian gene expression.

Prenatal testosterone (T) treatment leads to polycystic ovarian morphology, enhanced follicular recruitment/depletion, and increased estradiol secretion. This study addresses whether expression of key ovarian genes and microRNA are altered by prenatal T excess and whether changes are mediated by androgenic or estrogenic actions of T. Pregnant Suffolk ewes were treated with T or T plus the androgen receptor antagonist, flutamide (T+F) from d 30 to 90 of gestation.

Role of Dicer in female fertility.

Dicer is an RNAse III endonuclease that is essential for the biogenesis of microRNAs and small interfering RNAs. These small RNAs post-transcriptionally regulate mRNA gene expression through several mechanisms to affect key cellular events including proliferation, differentiation and apoptosis. Recently, the role of Dicer function in female reproductive tissues has begun to be elucidated through the use of knockout mouse models.

Dicer1 is essential for female fertility and normal development of the female reproductive system.

The ribonuclease III endonuclease, Dicer1 (also known as Dicer), is essential for the synthesis of the 19-25 nucleotide noncoding RNAs known as micro-RNAs (miRNAs). These miRNAs associate with the RNA-induced silencing complex to regulate gene expression posttranscriptionally by base pairing with 3'untranslated regions of complementary mRNA targets. Although it is established that miRNAs are expressed in the reproductive tract, their functional role and effect on reproductive disease remain unknown.