Variant PCGF1-PRC1 links PRC2 recruitment with differentiation-associated transcriptional inactivation at target genes

Sugishita, Hiroki; Kondo, Takashi; Ito, Shinsuke; Nakayama, Manabu; Yakushiji-Kaminatsui, Nayuta; Kawakami, Eiryo; Koseki, Haruhiko; Ohinata, Yasuhide; Sharif, Jafar; Harachi, Mio; Blackledge, Neil P.; Klose, Robert J.

doi:10.1038/s41467-021-24894-z

Cited by 28 publications

(29 citation statements)

References 35 publications

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“…The ncPRC1.1 complex, containing PCGF1 and the H3K36me2 histone demethylase KDM2B, is recruited globally to unmethylated CpG islands by KDM2B, through its CxxC-ZF domain, independently of its enzyme activity [ 24 , 25 , 26 , 27 , 28 ]. KDM2B is also required for ubiquitination by RING1B and recruitment of PRC2.2 (see below) depends on this ubiquitination by PRC1.1 (see Figure 2 right hand pathway) [ 21 , 26 , 27 , 28 , 29 , 30 , 31 , 32 ]. PRC2.2 produces the H3K27me mark recognised by the CBX protein in a cPRC1 complex, which can be recruited to enhance ubiquitination [ 20 , 21 , 32 ].…”

Section: Regulation Of Methylation Of Lysine 27 On Histonementioning

confidence: 99%

Histone Methylases and Demethylases Regulating Antagonistic Methyl Marks: Changes Occurring in Cancer

Taylor‐Papadimitriou

Burchell

2022

Cells

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Epigenetic regulation of gene expression is crucial to the determination of cell fate in development and differentiation, and the Polycomb (PcG) and Trithorax (TrxG) groups of proteins, acting antagonistically as complexes, play a major role in this regulation. Although originally identified in Drosophila, these complexes are conserved in evolution and the components are well defined in mammals. Each complex contains a protein with methylase activity (KMT), which can add methyl groups to a specific lysine in histone tails, histone 3 lysine 27 (H3K27), by PcG complexes, and H3K4 and H3K36 by TrxG complexes, creating transcriptionally repressive or active marks, respectively. Histone demethylases (KDMs), identified later, added a new dimension to histone methylation, and mutations or changes in levels of expression are seen in both methylases and demethylases and in components of the PcG and TrX complexes across a range of cancers. In this review, we focus on both methylases and demethylases governing the methylation state of the suppressive and active marks and consider their action and interaction in normal tissues and in cancer. A picture is emerging which indicates that the changes which occur in cancer during methylation of histone lysines can lead to repression of genes, including tumour suppressor genes, or to the activation of oncogenes. Methylases or demethylases, which are themselves tumour suppressors, are highly mutated. Novel targets for cancer therapy have been identified and a methylase (KMT6A/EZH2), which produces the repressive H3K27me3 mark, and a demethylase (KDM1A/LSD1), which demethylates the active H3K4me2 mark, are now under clinical evaluation.

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Section: Regulation Of Methylation Of Lysine 27 On Histonementioning

confidence: 99%

Histone Methylases and Demethylases Regulating Antagonistic Methyl Marks: Changes Occurring in Cancer

Taylor‐Papadimitriou

Burchell

2022

Cells

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“…The H3K27me3 marks are recognized by the CBX component and then PRC1 is recruited via the chromodomain of CBX proteins [ 46 , 51 , 52 ]. Recently, an alternative recruitment model, proposing that PRC1 is targeted to chromatin without pre-existing PRC2 and H3K27me3, was proposed in X chromosome inactivation and mouse embryonic stem cells [ 20 , 25 , 53 , 54 ]. Conversely, the H2AK119ub deposited by PRC1 facilitates the subsequent recruitment of PRC2 [ 54 ].…”

Section: Discussionmentioning

confidence: 99%

“…Recently, an alternative recruitment model, proposing that PRC1 is targeted to chromatin without pre-existing PRC2 and H3K27me3, was proposed in X chromosome inactivation and mouse embryonic stem cells [ 20 , 25 , 53 , 54 ]. Conversely, the H2AK119ub deposited by PRC1 facilitates the subsequent recruitment of PRC2 [ 54 ]. The recruitment model of PRC complexes in the cardiac sarcomere assembly is still unclear.…”

Section: Discussionmentioning

confidence: 99%

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PRC1 Stabilizes Cardiac Contraction by Regulating Cardiac Sarcomere Assembly and Cardiac Conduction System Construction

Peng

Feng

Zhang

et al. 2021

IJMS

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Cardiac development is a complex process that is strictly controlled by various factors, including PcG protein complexes. Several studies have reported the critical role of PRC2 in cardiogenesis. However, little is known about the regulation mechanism of PRC1 in embryonic heart development. To gain more insight into the mechanistic role of PRC1 in cardiogenesis, we generated a PRC1 loss-of-function zebrafish line by using the CRISPR/Cas9 system targeting rnf2, a gene encoding the core subunit shared by all PRC1 subfamilies. Our results revealed that Rnf2 is not involved in cardiomyocyte differentiation and heart tube formation, but that it is crucial to maintaining regular cardiac contraction. Further analysis suggested that Rnf2 loss-of-function disrupted cardiac sarcomere assembly through the ectopic activation of non-cardiac sarcomere genes in the developing heart. Meanwhile, Rnf2 deficiency disrupts the construction of the atrioventricular canal and the sinoatrial node by modulating the expression of bmp4 and other atrioventricular canal marker genes, leading to an impaired cardiac conduction system. The disorganized cardiac sarcomere and defective cardiac conduction system together contribute to defective cardiac contraction. Our results emphasize the critical role of PRC1 in the cardiac development.

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“…[45][46][47] In addition to the active recruitment of PcG complexes, as a passive mechanism of PcG activity, active transcription reduces PcG-mediated histone modifications, suggesting the role for transcription in the negative regulation of PcG activity. [43,48] To modulate regionalization during development, PcG proteins regulate the rostrocaudal axis of the body, including the central nervous system, by repression of Hox cluster genes in an evolutionally…”

Section: Polycomb-group Proteins Regulate Brain Regionalizationmentioning

confidence: 99%

Brain regionalization by Polycomb‐group proteins and chromatin accessibility

Eto

Kishi

2021

BioEssays

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During brain development, neural precursor cells (NPCs) in different brain regions produce different types of neurons, and each of these regions plays a different role in the adult brain. Therefore, precise regionalization is essential in the early stages of brain development, and irregular regionalization has been proposed as the cause of neurodevelopmental disorders. The mechanisms underlying brain regionalization have been well studied in terms of morphogen-induced expression of critical transcription factors for regionalization. NPC potential in different brain regions is defined by chromatin structures that regulate the plasticity of gene expression. Herein, we present recent findings on the importance of chromatin structure in brain regionalization, particularly with respect to its regulation by Polycomb-group proteins and chromatin accessibility.

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Variant PCGF1-PRC1 links PRC2 recruitment with differentiation-associated transcriptional inactivation at target genes

Cited by 28 publications

References 35 publications

Histone Methylases and Demethylases Regulating Antagonistic Methyl Marks: Changes Occurring in Cancer

Histone Methylases and Demethylases Regulating Antagonistic Methyl Marks: Changes Occurring in Cancer

PRC1 Stabilizes Cardiac Contraction by Regulating Cardiac Sarcomere Assembly and Cardiac Conduction System Construction

Brain regionalization by Polycomb‐group proteins and chromatin accessibility

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