Biology subjects

Arzate-Mejia, R. G.

Publications and source records attributed to Arzate-Mejia, R. G..

6 recordsLinked to original sources

bioRxiv2026

Paternal diet shapes paternal and maternal transcriptomes in the early embryo through parallel sperm-associated mechanisms

Life experiences in fathers can influence phenotypes in the offspring. While it is known that acquired paternal information can be transferred to descendants via the germline, how such transfer operates between sperm and embryo remains unclear. We examined the effects of low protein diet (LPD) on males of different genotypes and their hybrid offspring generated by reciprocal outcross and on their genome. We found that LPD induces genotype-specific effects in fathers and different phenotypes in their male and female offspring. Allele-specific analyses revealed that paternal LPD modifies paternal and maternal transcriptomes differently in early two-cell embryos. Changes in the paternal transcriptome overlap with the sperm transcriptome and are associated with sperm chromatin features, suggesting that sperm-inherited transcripts and chromatin states may shape the paternal transcriptome in the embryo. The maternal transcriptome, by contrast, is linked to sperm-derived small RNAs, consistent with a possible role of sperm-derived small RNAs in modulating maternal transcript levels in the embryo. Analyses of undifferentiated spermatogonia populations suggest that LPD-induced sperm states can originate from early stages of germ cells. These findings provide evidence that paternal experiences can influence the early embryo via processes involving each parental allele differently.

molecular biology↗

bioRxiv2026

Early life stress affects the transcription and chromatin accessibility of spermatogonial cells

Adversity in early life has lasting effects on the physiology and behavior of exposed individuals and their descendants. In mice, early-life stress alters the RNA content of adult sperm, and this RNA is sufficient to transmit some of the effects to the offspring who were never exposed. However, sperm cells are not yet formed during the early postnatal window in which the exposure occurs. Spermatogonial cells (SPGs), which give rise to them, are present at that time, but whether they respond to the exposure and maintain a molecular signature of it into adulthood is unknown. Here we show that early-life stress alters both the transcriptome and the chromatin accessibility of mouse SPGs, and that a molecular signature of the exposure remains detectable in adulthood. One day after exposure ended, the transcriptional response was extensive, with proliferation and nucleosome-organization programs coordinately up-regulated. In adulthood, the transcriptional response was modest and dominated by coordinately down-regulated gene programs. Single-cell profiling of the whole testis localized the adult response to spermatogonial stem cells (SSCs) and to genes involved in spermatogenesis. At the chromatin level, accessibility shifted one day after exposure at binding motifs for signal-responsive transcription factor families, and in adulthood at a different set of families, in both cases at primed enhancers. These data demonstrate that SPGs respond to an early postnatal environmental exposure and identify them as a candidate origin of the molecular changes later found in adult sperm.

genomics↗

bioRxiv2025

Circulating extracellular vesicles can transport stress signals to the male germline

Extracellular vesicles (EVs) play a key role in cell-cell communication by transporting bioactive molecules from donor to recipient cells across the body. While their involvement in somatic cells communication is well described, somatic-to-germ cells communication remains understudied. We show that small EVs (sEVs) can vehicle signals of early life stress (ELS) from circulation to sperm consequentially for the offspring. In mice, ELS persistently modifies RNA, lipids and metabolites in plasma sEVs. Chronic injection of plasma sEVs from ELS-exposed males alters the sperm transcriptome and is reflected in the transcriptome of embryos. This leads to metabolic dysfunctions in the adult offspring. These findings highlight a role of circulating sEVs in soma-to-germline communication relevant for the intergenerational transmission of ELS effects.

cell biology↗

bioRxiv2024

NanoTag - an IgG-free method for mapping DNA-protein interactions

Genome-wide profiling of DNA-protein interactions in cells can provide important information about mechanisms of gene regulation. Most current methods for genome-wide profiling of DNA-bound proteins, such as ChIP-seq and CUT&Tag, use conventional IgG antibodies to bind target protein(s), which limits their applicability to targets for which high affinity and high specificity antibodies are available. Here we describe NanoTag, a novel method derived from CUT&Tag that is IgG-free and uses a nanobody to profile DNA-protein interactions. NanoTag is based on an anti-GFP nanobody-Tn5 transposase fusion that allows mapping GFP-tagged proteins associated with chromatin in a fast and cost-effective manner. We demonstrate the utility of NanoTag by profiling the histone mark H3K4me3 via its binding partner TATA box-binding protein-associated factor 3 (TAF3) and the transcription factors Nanog and CTCF in mouse embryonic stem cells expressing GFP-tagged targets. For the targets examined, NanoTag data shows high correlation to CUT&Tag data and displays a similarly high signal-to-noise ratio. Overall, NanoTag provides a flexible, IgG-free and cost-effective method to generate high resolution DNA-binding profiles in cells or tissues.

molecular biology↗

bioRxiv2020

The global and promoter-centric 3D genome organization temporally resolved during a circadian cycle

Circadian gene expression is essential for organisms to adjust cellular responses and anticipate daily changes in the environment. In addition to its physiological importance, the clock circuit represents an ideal, temporally resolved, system to study transcription regulation. Here, we analysed changes in spatial mouse liver chromatin conformation using genome-wide and promoter-capture Hi-C alongside daily oscillations in gene transcription in mouse liver. We found circadian topologically associated domains switched assignments to the transcriptionally active, open chromatin compartment and the inactive compartment at different hours of the day while their boundaries stably maintain their structure over time. Individual circadian gene promoters displayed maximal chromatin contacts at times of peak transcriptional output and the expression of circadian genes and contacted transcribed regulatory elements, or other circadian genes, was phase-coherent. Anchor sites of promoter chromatin loops were enriched in binding sites for liver nuclear receptors and transcription factors, some exclusively present in either rhythmic or stable contacts. The circadian 3D chromatin maps provided here identify the scales of chromatin conformation that parallel oscillatory gene expression and protein factors specifically associated with circadian or stable chromatin configurations.

genomics↗

bioRxiv2019

In situ dissection of domain boundaries affect genome topology and gene transcription in Drosophila

The molecular mechanisms responsible for Topologically Associated Domains (TADs) formation are not yet fully understood. In Drosophila, it has been proposed that transcription is fundamental for TAD organization while the participation of genetic sequences bound by Architectural Proteins (APs) remains controversial. Here, we investigate the contribution of domain boundaries to TAD organization and the regulation of gene expression at the Notch gene locus in Drosophila. We find that deletion of domain boundaries results in TAD fusion and long-range topological defects that are accompanied by loss of APs and RNA Pol II chromatin binding as well as defects in transcription. Together, our results provide compelling evidence on the contribution of discrete genetic sequences bound by APs and RNA Pol II in the partition of the genome into TADs and in the regulation of gene expression in Drosophila.

genomics↗