RNF12 Activates Xist and Is Essential for X Chromosome Inactivation

Barakat, Tahsin Stefan; Gunhanlar, Nilhan; Gontan, Cristina; Mulugeta, Eskeatnaf; Ghazvini, Mehrnaz; Boers, Ruben; Kenter, Annegien; Rentmeester, Eveline; Grootegoed, J. Anton; Gribnau, Joost

doi:10.1371/journal.pgen.1002001

Cited by 135 publications

(215 citation statements)

References 29 publications

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“…58 Furthermore, Rnf12 seems essential for XCI, because the majority of Rnf12 -/-female mES did not undergo XCI during differentiation. 59 Rnf12 was shown to achieve this regulation by binding enrichment at the Xist but not Tsix promoter. Another report supported the finding that Rnf12 is essential for XCI, as the maternally transmitted allele with an Rnf12 deletion caused embryonic lethality.…”

Section: Rnf12 An Ubiquitin Ligase Involved In X-chromosome Inactivamentioning

confidence: 98%

The lesser known story of X chromosome reactivation

et al. 2012

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Section: Rnf12 An Ubiquitin Ligase Involved In X-chromosome Inactivamentioning

confidence: 98%

The lesser known story of X chromosome reactivation

et al. 2012

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“…In the case of Xist, however, nearly all stem cell factors tested so far, bind to one or more sites within or around the Xist gene ( Figure 2, Table 1) [34 ,37-39,41,42]. One of these binding sites (in Xist intron 1) has recently been tested for functionality by deletion and was found to have only a minor effect, if any, on Xist expression during differentiation [43]. This suggests either that only a subset of binding sites are functional, or that the sites and therefore also the factors that occupy them, act in a redundant fashion.…”

Section: Developmental Regulation Of X Inactivationmentioning

confidence: 99%

Role and control of X chromosome dosage in mammalian development

Schulz¹,

Heard²

2013

Current Opinion in Genetics & Development

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Many species have evolved sex chromosomes with highly divergent gene content, such as the X and Y chromosomes in mammals. As most non sex-specific genes probably need to be expressed at similar levels in males and females, dosage compensation mechanisms are in place to equalize the gene dosage between the sexes, and possibly also between sex chromosomes and autosomes. In mammals, one out of two X chromosomes is inactivated early during development in a process called X-chromosome inactivation that has been investigated intensively in the 50 years since it was discovered. Less is known about the potential functional roles of X-linked gene dosage, for example in controlling development in a sexspecific manner. In this review, we discuss the evolution of dosage compensation and how it is controlled during embryogenesis of mammals. In addition we will summarize evidence on the potential role of X chromosome number during early development. IntroductionIn many species, sex is determined by sex chromosome composition, such as XY and XX in male and female mammals. The X and Y chromosomes presumably evolved from a pair of autosomes, one of which (the proto-Y) acquired a sex determining gene and subsequently accumulated male beneficial genes. To permanently link these genes to the male sex, the Y chromosome had to cease recombining with the X during meiosis, and this facilitated a progressive loss of Y-linked genes (reviewed in [1]). Therefore for most X-linked genes, only one copy remains, on the X, and this creates a dosage imbalance, both with respect to interacting autosomal genes and between the sexes (XX versus XY). To resolve this dosage imbalance, a variety of dosage compensation mechanisms have evolved (reviewed in [2]). The first step in compensating the loss of Y-linked genes is probably the upregulation of their Xlinked homologs (Ohno's hypothesis [3]). In the wellstudied example of Drosophila this upregulation is restricted to males, thereby restoring both dosage equality between the X chromosome and autosomes, as well as between the sexes. In contrast, worms (Caenorhabditis elegans) and mammals are thought to upregulate the X chromosome in both sexes and therefore require additional mechanisms to balance X-linked gene dosage between males and females. To achieve this, worms downregulate both X's in hermaphrodites (XX), while mammals, on which we focus in this review, silence one of the two X chromosomes in each female cell in a process called Xchromosome inactivation (XCI). Albeit widespread, the extent of dosage compensation between the sexes varies considerably among species. In birds for example, dosage compensation of Z-linked genes is only partial, as males (ZZ) express 1.2-1.4-fold higher levels compared to females (ZW) [2].Although in mammals, dosage compensation for most genes on the X is probably vital, dosage differences might also play a functional role at several levels. In particular, genes that escape X inactivation are thought to contribute to the phenotypic differences between the sexes [4]...

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“…Cette réactivation pourrait être liée à la répression de Xist par les facteurs de pluripotence Oct4 (octamer-binding transcription factor 4) et Nanog dans les cellules préépiblastiques [30]. Ces facteurs agiraient directement en réprimant Xist par leur liaison sur le premier intron, et indirectement en contrôlant des activateurs de Xist, comme RNF12 ou l'antisens Tsix [31,32,35]. Aux jours 4,5-5 de gestation, les deux chromosomes X deviennent actifs.…”

Section: Empreinte(s) Maternelle(s) ?unclassified