Dosage compensation in human pre‐implantation embryos: X‐chromosome inactivation or dampening?

Saiba, Roni; Arava, Maniteja; Gayen, Srimonta

doi:10.15252/embr.201846294

Cited by 18 publications

(15 citation statements)

References 9 publications

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“…However, the pattern of XCI in other mammalian species is not clear yet. For example, in preimplantation human and bovine embryos, XCI does not follow an imprinted inactivation as in the mouse, and the precise mechanism of dosage compensation continues being debated ( Bermejo-Alvarez et al, 2010 ; Saiba et al, 2018 ). Nonetheless, the effects of paternal haploidy on expression during early embryogenesis of X chromosome and imprinted genes has not yet been evaluated in bovine species.…”

Section: Discussionmentioning

confidence: 99%

Dysregulated Gene Expression of Imprinted and X-Linked Genes: A Link to Poor Development of Bovine Haploid Androgenetic Embryos

Águila

Suzuki

Hill

et al. 2021

Front. Cell Dev. Biol.

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Mammalian uniparental embryos are efficient models for genome imprinting research and allow studies on the contribution of the paternal and maternal genomes to early embryonic development. In this study, we analyzed different methods for production of bovine haploid androgenetic embryos (hAE) to elucidate the causes behind their poor developmental potential. Results indicate that hAE can be efficiently generated by using intracytoplasmic sperm injection and oocyte enucleation at telophase II. Although androgenetic haploidy does not disturb early development up to around the 8-cell stage, androgenetic development is disturbed after the time of zygote genome activation and hAE that reach the morula stage are less capable to reach the blastocyst stage of development. Karyotypic comparisons to parthenogenetic- and ICSI-derived embryos excluded chromosomal segregation errors as causes of the developmental constraints of hAE. However, analysis of gene expression indicated abnormal levels of transcripts for key long non-coding RNAs involved in X chromosome inactivation and genomic imprinting of the KCNQ1 locus, suggesting an association with X chromosome and some imprinted loci. Moreover, transcript levels of methyltransferase 3B were significantly downregulated, suggesting potential anomalies in hAE establishing de novo methylation. Finally, the methylation status of imprinted control regions for XIST and KCNQ1OT1 genes remained hypomethylated in hAE at the morula and blastocyst stages, confirming their origin from spermatozoa. Thus, our results exclude micromanipulation and chromosomal abnormalities as major factors disturbing the normal development of bovine haploid androgenotes. In addition, although the cause of the arrest remains unclear, we have shown that the inefficient development of haploid androgenetic bovine embryos to develop to the blastocyst stage is associated with abnormal expression of key factors involved in X chromosome activity and genomic imprinting.

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Section: Discussionmentioning

confidence: 99%

Dysregulated Gene Expression of Imprinted and X-Linked Genes: A Link to Poor Development of Bovine Haploid Androgenetic Embryos

Águila

Suzuki

Hill

et al. 2021

Front. Cell Dev. Biol.

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“…The presence of an initial biallelic X-chromosome dampening during the human female preimplantation development is an interesting and perhaps provoking thesis under some prevailing dogma in the XCI field, and as such needs to get challenged and tested 14 . However, we did not find the claims, nor the analysis, by Moreira de Mello et al 5 convincing.…”

Section: Resultsmentioning

confidence: 99%

Expression reduction of biallelically transcribed X-linked genes during the human female preimplantation development

Reinius

Sandberg

2019

Preprint

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Our previous single-cell RNA-seq data from human preimplantation embryos showed that female X-chromosome mRNA levels become partly dose compensated during the timespan between zygotic genome activation (ZGA) and implantation. At the same time, XIST RNA is expressed from, and forms clouds in proximity to, both X-chromosome copies and biallelic expression of other X-linked genes persists. We proposed that X-chromosome transcription is transiently lowered on both alleles before X-chromosome inactivation (XCI) takes place. This notion was recently challenged in a reanalysis performed by Moreira de Mello et al, claiming to provide evidence against biallelic expression dampening and that instead proper XCI was responsible for the observed dosage compensation. Here we have addressed this reanalysis and highlighted methodological issues, and we conclude a current lack of evidence against biallelic X-chromosome dampening.

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“…Different from the mouse, in human preimplantation embryos, the X p does not undergo imprinted inactivation; however, due to their limited availability, different sources and culture conditions, the precise mechanism of dosage compensation in our species remains still debated [Saiba et al, 2018]. Recently, 2 differing models ( Fig.…”

Section: From Zygote To Blastocystmentioning

confidence: 99%

X-Chromosome Inactivation during Preimplantation Development and in Pluripotent Stem Cells

Rebuzzini

Zuccotti

Garagna

2020

Cytogenet Genome Res

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X dosage compensation between XX female and XY male mammalian cells is achieved by a process known as X-chromosome inactivation (XCI). XCI initiates early during preimplantation development in female cells, and it is subsequently stably maintained in somatic cells. However, XCI is a reversible process that occurs in vivo in the inner cell mass of the blastocyst, in primordial germ cells or in spermatids during reprogramming. Erasure of transcriptional gene silencing can occur though a mechanism named X-chromosome reactivation (XCR). XCI and XCR have been substantially deciphered in the mouse, whereas they still remain debated in the human. In this review, we summarized the recent advances in the knowledge of X-linked gene dosage compensation during mouse and human preimplantation development and in pluripotent stem cells.

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Dosage compensation in human pre‐implantation embryos: X‐chromosome inactivation or dampening?

Abstract: Recent studies support either X‐dampening or X‐inactivation as the mechanism of dosage compensation in human embryos. The data and possible underlying causes for these conflicting models are discussed here.

Cited by 18 publications

References 9 publications

Dysregulated Gene Expression of Imprinted and X-Linked Genes: A Link to Poor Development of Bovine Haploid Androgenetic Embryos

Dysregulated Gene Expression of Imprinted and X-Linked Genes: A Link to Poor Development of Bovine Haploid Androgenetic Embryos

Expression reduction of biallelically transcribed X-linked genes during the human female preimplantation development

X-Chromosome Inactivation during Preimplantation Development and in Pluripotent Stem Cells

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