The FBXL10/KDM2B Scaffolding Protein Associates with Novel Polycomb Repressive Complex-1 to Regulate Adipogenesis

Inagaki, Takeshi; Iwasaki, Syoichi; Matsumura, Yoshihiro; Kawamura, Takeshi; Tanaka, Toshiya; Abe, Yohei; Yamasaki, Ayumu; Tsurutani, Yuya; Yoshida, Ayano; Chikaoka, Yoko; Nakamura, Kenya; Magoori, Kenta; Nakaki, Ryo; Osborne, Timothy F.; Fukami, Kiyoko; Aburatani, Hiroyuki; Kodama, Tatsuhiko; Sakai, Juro

doi:10.1074/jbc.m114.626929

Cited by 39 publications

(53 citation statements)

References 59 publications

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“…We first examined the distribution of KDM2B in the tissues of adult mice. KDM2B was highly expressed in the brain ( Fig EV1A) as previously reported (Inagaki et al, 2015). To investigate the role of KDM2B in skeletal muscle, we first checked its expression using a C2C12 myoblast cell line.…”

Section: Kdm2b Is Expressed In the Early Phase Of Skeletal Muscle Difsupporting

confidence: 56%

“…However, KDM2B can also decrease cancer cell proliferation by inhibiting the expression of oncogenes (Yan et al, 2018). Other than regulating cell proliferation and thereby tumor biology, KDM2B inhibits adipogenesis as part of polycomb repressive complex 1 (PRC1), but in a demethylaseindependent manner (Inagaki et al, 2015). However, the role of KDM2B histone demethylase in myogenic differentiation remains unknown.…”

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confidence: 99%

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SRF is a non-histone methylation target of KDM2B and SET7 in the regulation of myogenesis

Kook

Joung

Kang

et al. 2020

Preprint

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Demethylation of histone lysines, one of the most important modifications in transcriptional regulation, is associated with various physiological states. KDM2B is a histone H3K4, H3K36, and H3K79 demethylase associated with the repression of transcription. Here, we present a novel mechanism by which KDM2B demethylates serum response factor (SRF) K165 to negatively regulate muscle differentiation, which is counteracted by histone methyltransferase SET7. We show that KDM2B inhibited skeletal muscle differentiation by inhibiting the transcription of SRF-dependent genes. Both KDM2B and SET7 regulated the balance of SRF K165 methylation. SRF K165 methylation was required for the transcriptional activation of SRF and for the promoter occupancy of SRF-dependent genes.SET7 inhibitors blocked muscle cell differentiation. Taken together, these data indicate that SRF is a non-histone target of KDM2B and that the methylation balance of SRF maintained by KDM2B and SET7 plays an important role in muscle cell differentiation.

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Section: Kdm2b Is Expressed In the Early Phase Of Skeletal Muscle Difsupporting

confidence: 56%

mentioning

confidence: 99%

SRF is a non-histone methylation target of KDM2B and SET7 in the regulation of myogenesis

Kook

Joung

Kang

et al. 2020

Preprint

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“…KDM2B contains multiple functional domains, including the JmjC histone demethylase domain, a DNA-binding CxxC zinc finger, an F-box domain, a PHD finger, and eight leucine-rich repeats (LRRs). The F-box and the LRR domain are required for variant polycomb repressor complex 1 (PRC1) recruitment and assembly (Farcas et al, 2012; He et al, 2013; Inagaki et al, 2015; Wu et al, 2013). To decipher how KDM2B exerts its function in cortical development, we carried out rescue experiments using in utero electroporation (Figure 6A-6D).…”

Section: Resultsmentioning

confidence: 99%

Long Non-Coding RNA LncKdm2b Regulates Cortical Neuronal Differentiation by Cis-Activating Kdm2b

Shen

Zhang

et al. 2018

Preprint

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13The mechanisms underlying spatial and temporal control of cortical neurogenesis of the 14 brain are largely elusive. Long non-coding RNAs (lncRNAs) have emerged as essential 15 cell fate regulators. Here we found LncKdm2b (also known as Kancr), a lncRNA 16 divergently transcribed from a bidirectional promoter of Kdm2b, is transiently expressed 17 during early differentiation of cortical projection neurons. Interestingly, Kdm2b's 18 transcription is positively regulated in cis by LncKdm2b, which has intrinsic-activating 19 function and facilitates a permissive chromatin environment at the Kdm2b's promoter by 20 associating with hnRNPAB. Lineage tracing experiments and phenotypic analyses 21 indicated LncKdm2b and Kdm2b are crucial in proper differentiation and migration of 22 cortical projection neurons. Moreover, KDM2B exerts its role relying on its leucine-rich 23 repeats (LRR) but independent of its PRC1-related function. These observations unveiled 24 a lncRNA-dependent machinery in regulating cortical neuronal differentiation.Recent studies indicate a few long non-coding RNAs could be essential cell fate regulators 50 in development (Grote et al., 2013; Klattenhoff et al., 2013). Long non-coding RNAs 51 3 (lncRNAs), defined as RNAs longer than 200 nucleotides but lacking protein-coding 52 potentials, are abundant in brain and display cell-type-, and developmental stage-specific 53 expression patterns compared to protein-coding transcripts (Aprea et al., 2013; Belgard 54 et al., 2011; Mercer et al., 2010; Molyneaux et al., 2015). LncRNAs may regulate gene 55 transcription by recruiting transcription factors, RNA-binding proteins and chromatin-56 remodeling machineries to the site of transcription and creating a locus-specific 57 environment (Lin et al., 2014; Ng et al., 2013; Wang et al., 2015). LncRNAs are often 58 derived from bidirectional promoters, such that initiating Pol II can generate divergently-59 oriented transcripts simultaneously, the sense (protein-coding mRNA) direction or the 60 upstream-antisense (divergent non-coding) direction, with these mRNA/divergent lncRNA 61 pairs having coordinated expression (Lepoivre et al., 2013; Scruggs and Adelman, 2015; 62 Sigova et al., 2013). Moreover, the transcription of divergent lncRNAs could affect the 63 expression of their neighboring protein-coding transcripts in cis (Luo et al., 2016; Ørom et 64 al., 2010). Anti-sense promoters could serve as platforms for transcription factor (TF) 65 binding and facilitate establishment of proper chromatin architecture to regulate sense-66 strand mRNA expression (Scruggs and Adelman, 2015; Scruggs et al., 2015). Although 67 divergent lncRNAs are prevalent in both embryonic and adult nervous system, only a few 68 functional divergent lncRNAs have been characterized, including roles of Emx2OS and in 69 regulating the expressions of their neighboring protein-coding transcripts Emx2, an 70 essential cortical RGPC gene (Noonan et al., 2003; Spigoni et al., 2010). Furthermore, 71 these are largely in vitro stu...

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“…Interestingly, KDM2B-dependent adipogenesis inhibition is independent from the demethylase activity of the protein; however, its F-box and leucine-rich repeat domains are required for recruiting a noncanonical PRC1 containing the RING1B, SKP1, PCGF1, and BCOR proteins [75].…”

Section: Kdm2 Cluster (Fbxl Subfamily)mentioning

confidence: 99%

Lysine-Specific Histone Demethylases Contribute to Cellular Differentiation and Carcinogenesis

Verde

Querol-Paños²,

Cebrià-Costa³

et al. 2017

Epigenomes

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Histone modifications regulate chromatin structure, gene transcription, and other nuclear processes. Among the histone modifications, methylation has been considered to be a stable, irreversible process due to the slow turnover of methyl groups in chromatin. However, the discovery of three different classes of lysine-specific demethylases-KDM1, Jumonji domain-containing demethylases, and lysyl oxidase-like 2 protein-has drastically changed this view, suggesting a role for dynamic histone methylation in different biological process. In this review, we describe the different mechanisms that these enzymes use to remove lysine histone methylation and discuss their role during physiological (cell differentiation) and pathological (carcinogenesis) processes.

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The FBXL10/KDM2B Scaffolding Protein Associates with Novel Polycomb Repressive Complex-1 to Regulate Adipogenesis

Cited by 39 publications

References 59 publications

SRF is a non-histone methylation target of KDM2B and SET7 in the regulation of myogenesis

SRF is a non-histone methylation target of KDM2B and SET7 in the regulation of myogenesis

Long Non-Coding RNA LncKdm2b Regulates Cortical Neuronal Differentiation by Cis-Activating Kdm2b

Lysine-Specific Histone Demethylases Contribute to Cellular Differentiation and Carcinogenesis

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