A permissive chromatin state regulated by ZFP281-AFF3 in controlling the imprinted Meg3 polycistron

Wang, Yan; Shen, Yang; Dai, Qian; Yang, Qian; Zhang, Yue; Wang, Xin; Xie, Wei; Luo, Zhuojuan; Lin, Chengqi

doi:10.1093/nar/gkw1051

Cited by 48 publications

(62 citation statements)

References 34 publications

(57 reference statements)

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“…Zfp281 cooperates with epigenetic control mechanisms, such as histone acetylation and methylation complexes, to exert transcriptional activity in ESCs or during epiblast maturation. [36][37][38] According to the RNA-Seq analysis results, we found that more genes with altered expression in Zfp281-knockout CD4 + T cells tended to be upregulated ( Fig. 5a), suggesting that Zfp281 might function as a repressor in CD4 + T cells.…”

Section: Discussionmentioning

confidence: 88%

The transcription factor Zfp281 sustains CD4+ T lymphocyte activation through directly repressing Ctla-4 transcription

Guo

Xue

et al. 2019

Cell Mol Immunol

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The expression of coinhibitory receptors, such as CTLA-4, on effector T cells is a key mechanism for the negative regulation of T-cell activation. However, the transcriptional regulation of CTLA-4 is not well understood. Zfp281, a C2H2 zinc finger protein, is a negative regulator of pluripotency maintenance of embryonic stem cells. Nevertheless, the function of Zfp281 in differentiated cells has not been studied. We generated Zfp281 conditional knockout mice in which the function of the Zfp281 gene was conditionally disrupted by the Cd4 Cre transgene to study its impact on T cell function. Zfp281 had no effect on T-cell development, but CD4 + T cell activation and cytokine production were impaired due to diminished T-cell receptor signaling. Furthermore, Zfp281 deficiency inhibited in vivo T cell responses to Listeria monocytogenes infection. Using genome-wide expression profiling assays, we determined that Zfp281 repressed Ctla-4 expression by directly binding to GC-rich sites in its promoter, which inhibited the negative feedback of T cell activation. In line with this result, CTLA-4 blockade and shRNA knockdown partly rescued the reduced cytokine production caused by Zfp281 deficiency. These findings indicate that Zfp281 sustains CD4 + T lymphocyte activation by directly repressing Ctla-4 transcription.

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Section: Discussionmentioning

confidence: 88%

The transcription factor Zfp281 sustains CD4+ T lymphocyte activation through directly repressing Ctla-4 transcription

Guo

Xue

et al. 2019

Cell Mol Immunol

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“…In order to understand how USP9X may act upon target genes, we searched for transcription factor motifs enrichment using the oPOSSUM web-based platform. We revealed that genes deregulated in Usp9X KD cells were enriched in their promoter for DNA motifs of core pluripotency transcription factors, including KLF4, ZFP281 and MYC ( Supplementary Table 4G-H) [56][57][58]. This suggests that USP9X transcriptional targets are also regulated by pluripotency factors.…”

Section: Usp9x Regulates Pluripotency Transition and Its Depletion Comentioning

confidence: 87%

USP9X deubiquitinase couples the pluripotency network and cell metabolism to regulate ESC differentiation potential

Dieuleveult

Salataj

Ransy

et al. 2020

Preprint

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Embryonic stem cells (ESC) have the unique ability to differentiate into all three germ cell layers. ESC transition through different states of pluripotency in response to growth factor signals and environmental cues before becoming terminally differentiated. Here, we demonstrated, by a multi-omic strategy, that the deubiquitinase USP9X regulates the developmental potential of ESC, and their transition from a naive to a more developmentally advance, or primed, state of pluripotency. We show that USP9X facilitates developmental gene expression and induces modifications of the mitochondrial bioenergetics, including decreased routing of pyruvate towards its oxidation and reduced respiration. In addition, USP9X binds to the pluripotency factor ESRRB, regulates its abundance and the transcriptional levels of a subset of its target genes. Finally, under permissive culture conditions, depletion of Usp9X accelerates cell differentiation in all cell lineages. We thus identified a new regulator of naive pluripotency and show that USP9X couples ESRRB pluripotency transcriptional network and cellular metabolism, both of which are important for ESC fate and pluripotency. Words: 164

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“…At the somatic DMR of the Meg3 lncRNA gene at the Dlk1-Dio3 imprinted domain, the KRAB domain zinc finger protein ZFP281 facilitates promoter activity on the maternal chromosome both in embryonic and trophoblast cells. It recruits MLL protein complexes to the chromatin, which brings about H3K4me3, and also interacts with AFF3, a component of the transcription elongation complex [103][104][105].…”

Section: Protection Of Icrs Against De Novo Dna Methylationmentioning

confidence: 99%

Stability and Lability of Parental Methylation Imprints in Development and Disease

Farhadova

Gómez-Velázquez

Feil

2019

Genes

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DNA methylation plays essential roles in mammals. Of particular interest are parental methylation marks that originate from the oocyte or the sperm, and bring about mono-allelic gene expression at defined chromosomal regions. The remarkable somatic stability of these parental imprints in the pre-implantation embryo—where they resist global waves of DNA demethylation—is not fully understood despite the importance of this phenomenon. After implantation, some methylation imprints persist in the placenta only, a tissue in which many genes are imprinted. Again here, the underlying epigenetic mechanisms are not clear. Mouse studies have pinpointed the involvement of transcription factors, covalent histone modifications, and histone variants. These and other features linked to the stability of methylation imprints are instructive as concerns their conservation in humans, in which different congenital disorders are caused by perturbed parental imprints. Here, we discuss DNA and histone methylation imprints, and why unravelling maintenance mechanisms is important for understanding imprinting disorders in humans.

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A permissive chromatin state regulated by ZFP281-AFF3 in controlling the imprinted Meg3 polycistron

Cited by 48 publications

References 34 publications

The transcription factor Zfp281 sustains CD4+ T lymphocyte activation through directly repressing Ctla-4 transcription

The transcription factor Zfp281 sustains CD4+ T lymphocyte activation through directly repressing Ctla-4 transcription

USP9X deubiquitinase couples the pluripotency network and cell metabolism to regulate ESC differentiation potential

Stability and Lability of Parental Methylation Imprints in Development and Disease

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