Cleavage-embryo genes and transposable elements are regulated by histone variant H2A.X

Sun, Kai-yi; Guo, Shimeng; Cheng, Guiping; Yin, Ying; He, Ximiao; Zhou, Li-Quan

doi:10.1262/jrd.2021-065

Cited by 5 publications

(3 citation statements)

References 42 publications

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“…To control Young REs, we have evolved a detection and suppression system. However, while H2A.X both regulates gene activation and provides some level of Young RE regulation [ 69 ] at EGA, Young REs, could take the window of opportunity immediately after EGA to express and transpose before silencing mechanisms come fully into operation. These counter-acting processes could then quite probably generate within-clone, between-cell heterogeneity such that some cells are more heavily affected by RE damage than others.…”

Section: Discussionmentioning

confidence: 99%

A new human embryonic cell type associated with activity of young transposable elements allows definition of the inner cell mass

et al. 2023

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There remains much that we do not understand about the earliest stages of human development. On a gross level, there is evidence for apoptosis, but the nature of the affected cell types is unknown. Perhaps most importantly, the inner cell mass (ICM), from which the foetus is derived and hence of interest in reproductive health and regenerative medicine, has proven hard to define. Here, we provide a multi-method analysis of the early human embryo to resolve these issues. Single-cell analysis (on multiple independent datasets), supported by embryo visualisation, uncovers a common previously uncharacterised class of cells lacking commitment markers that segregates after embryonic gene activation (EGA) and shortly after undergo apoptosis. The discovery of this cell type allows us to clearly define their viable ontogenetic sisters, these being the cells of the ICM. While ICM is characterised by the activity of an Old non-transposing endogenous retrovirus (HERVH) that acts to suppress Young transposable elements, the new cell type, by contrast, expresses transpositionally competent Young elements and DNA-damage response genes. As the Young elements are RetroElements and the cells are excluded from the developmental process, we dub these REject cells. With these and ICM being characterised by differential mobile element activities, the human embryo may be a “selection arena” in which one group of cells selectively die, while other less damaged cells persist.

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Section: Discussionmentioning

confidence: 99%

A new human embryonic cell type associated with activity of young transposable elements allows definition of the inner cell mass

et al. 2023

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“…The incapacity of sex body formation by condensation of H2A.X-deficient spermatocytes from X and Y chromosome is proposed as the cause of infertility, leading to failure of initiating Meiotic Sex Chromosome Inactivation (MSCI) [ 43 ]. In addition, H2A.X can regulate the proper expression of Zygotic Genome Activation ( ZGA ) genes and Transposable Elements (TE) to allow the establishment of totipotency of mESCs [ 44 ]. In human, γ-H2A.X was determined to regulate the fate of human Pluripotent Stem Cells (hPSCs) and progenitor cells.…”

Section: The 19 Histone H2a Variantsmentioning

confidence: 99%

Roles of Histone H2A Variants in Cancer Development, Prognosis, and Treatment

Lai,

Chan

2024

IJMS

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Histones are nuclear proteins essential for packaging genomic DNA and epigenetic gene regulation. Paralogs that can substitute core histones (H2A, H2B, H3, and H4), named histone variants, are constitutively expressed in a replication-independent manner throughout the cell cycle. With specific chaperones, they can be incorporated to chromatin to modify nucleosome stability by modulating interactions with nucleosomal DNA. This allows the regulation of essential fundamental cellular processes for instance, DNA damage repair, chromosomal segregation, and transcriptional regulation. Among all the histone families, histone H2A family has the largest number of histone variants reported to date. Each H2A variant has multiple functions apart from their primary role and some, even be further specialized to perform additional tasks in distinct lineages, such as testis specific shortH2A (sH2A). In the past decades, the discoveries of genetic alterations and mutations in genes encoding H2A variants in cancer had revealed variants’ potentiality in driving carcinogenesis. In addition, there is growing evidence that H2A variants may act as novel prognostic indicators or biomarkers for both early cancer detection and therapeutic treatments. Nevertheless, no studies have ever concluded all identified variants in a single report. Here, in this review, we summarize the respective functions for all the 19 mammalian H2A variants and their roles in cancer biology whilst potentiality being used in clinical setting.

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“…Another identified H2A variant is H2A.X, which plays a role in DNA repair [182,183]. In mammals, H2A.X shares up to 95% sequence similarities with canonical H2A and is highly conserved across species [184]. H2A.X contains a unique SQ motif at its C-terminus and is invariant in sequence and position relative to its C-terminus across species [185,186].…”

Section: Functional Diversity Of Histone Variants In the Activation O...mentioning

confidence: 99%

The Dynamics of Histone Modifications during Mammalian Zygotic Genome Activation

Sotomayor-Lugo,

Iglesias-Barrameda,

Castillo-Aleman

et al. 2024

IJMS

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Mammalian fertilization initiates the reprogramming of oocytes and sperm, forming a totipotent zygote. During this intricate process, the zygotic genome undergoes a maternal-to-zygotic transition (MZT) and subsequent zygotic genome activation (ZGA), marking the initiation of transcriptional control and gene expression post-fertilization. Histone modifications are pivotal in shaping cellular identity and gene expression in many mammals. Recent advances in chromatin analysis have enabled detailed explorations of histone modifications during ZGA. This review delves into conserved and unique regulatory strategies, providing essential insights into the dynamic changes in histone modifications and their variants during ZGA in mammals. The objective is to explore recent advancements in leading mechanisms related to histone modifications governing this embryonic development phase in depth. These considerations will be useful for informing future therapeutic approaches that target epigenetic regulation in diverse biological contexts. It will also contribute to the extensive areas of evolutionary and developmental biology and possibly lay the foundation for future research and discussion on this seminal topic.

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Cleavage-embryo genes and transposable elements are regulated by histone variant H2A.X

Cited by 5 publications

References 42 publications

A new human embryonic cell type associated with activity of young transposable elements allows definition of the inner cell mass

A new human embryonic cell type associated with activity of young transposable elements allows definition of the inner cell mass

Roles of Histone H2A Variants in Cancer Development, Prognosis, and Treatment

The Dynamics of Histone Modifications during Mammalian Zygotic Genome Activation

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