The genome of eukaryotes is highly organized within the cell nucleus, this organization per se elicits gene regulation and favors other mechanisms like cell memory throughout histones and their post-translational modifications. In highly specialized cells, like sperm, the genome is mostly organized by protamines, yet a significant portion of it remains organized by histones. This protamine-histone-DNA organization, known as sperm epigenome, is established during spermiogenesis. Specific histones and their posttranslational modifications are retained at specific genomic sites and during embryo development these sites recapitulate their histone profile that harbored in the sperm nucleus. It is known that histones are the conduit of epigenetic memory from cell to cell, hence histones in the sperm epigenome may have a role in transmitting epigenetic memory from the sperm to the embryo. However, the exact function and mechanism of histone retention remains elusive. During spermatogenesis, most of the histones that organize the genome are replaced by protamines and their retention at specific regions may be deeply intertwined with the eviction and replacement mechanism. In this review we will cover some relevant aspects of histone replacement that in turn may help us to contextualize histone retention. In the end, we focus on the architectonical protein CTCF that is, so far, the only factor that has been directly linked to the histone retention process.
CTCF is an architectonical protein that organizes the genome inside the cell nucleus in almost all eukaryotic cells. There is evidence that CTCF plays a critical role during spermatogenesis as its depletion produces abnormal sperm and infertility. However, the defects produced by the absence of CTCF throughout spermatogenesis have not been characterized. In this work, we performed single cell RNA sequencing in spermatogenic cells without CTCF. We uncovered defects in transcriptional programs that explain the severity of the damage in the produced sperm. At early stages of spermatogenesis, transcriptional alterations are mild. As germ cells go throughout the specialization stage or spermiogenesis, transcriptional profiles become more altered. We found spermatid defects that support the alterations in the transcriptional profiles, and thus we conclude that CTCF depletion alters several transcriptional profiles mostly during spermiogenesis. Our data highlights the importance of CTCF at the different stages of spermatogenesis.
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