Reprogramming CBX8-PRC1 function with a positive allosteric modulator

Suh, Junghyun L.; Bsteh, Daniel; Hart, Bryce; Si, Yibo; Weaver, Tyler; Pribitzer, Carina; Lau, Roy; Soni, Shivani; Ogana, Heather; Rectenwald, Justin M.; Norris, Jacqueline L.; Cholensky, Stephanie H.; Sagum, Cari A.; Umana, Jessica D.; Li, Dongxu; Hardy, Brian; Bedford, Mark T.; Mumenthaler, Shannon M.; Lenz, Heinz‐Josef; Kim, Yong-Mi; Wang, Gang Greg; Pearce, Ken H.; James, Lindsey I.; Kireev, Dmitri; Musselman, Catherine A.; Frye, Stephen V.; Bell, Oliver

doi:10.1016/j.chembiol.2021.10.003

Cited by 15 publications

(7 citation statements)

References 88 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Elegant tethering systems in mESC have shown that Cbx7-TetR and Rybp-TetR recruitment can induce gene repression [ 178 ]. Interestingly, gene repression and TetR-Cbx7 signal persist in the absence of the initial recruitment stimulus, even a dozen division cycles after the release of the chimeric proteins [ 178 , 215 ]. On the contrary, TetR- Rybp release causes gene reactivation and the displacement of PRC2 from chromatin [ 178 ].…”

Section: De Novo Targeting In Homeostasis and Replication: I...mentioning

confidence: 99%

De Novo Polycomb Recruitment and Repressive Domain Formation

Hernández-Romero

Valdés

2022

Epigenomes

View full text Add to dashboard Cite

Every cell of an organism shares the same genome; even so, each cellular lineage owns a different transcriptome and proteome. The Polycomb group proteins (PcG) are essential regulators of gene repression patterning during development and homeostasis. However, it is unknown how the repressive complexes, PRC1 and PRC2, identify their targets and elicit new Polycomb domains during cell differentiation. Classical recruitment models consider the pre-existence of repressive histone marks; still, de novo target binding overcomes the absence of both H3K27me3 and H2AK119ub. The CpG islands (CGIs), non-core proteins, and RNA molecules are involved in Polycomb recruitment. Nonetheless, it is unclear how de novo targets are identified depending on the physiological context and developmental stage and which are the leading players stabilizing Polycomb complexes at domain nucleation sites. Here, we examine the features of de novo sites and the accessory elements bridging its recruitment and discuss the first steps of Polycomb domain formation and transcriptional regulation, comprehended by the experimental reconstruction of the repressive domains through time-resolved genomic analyses in mammals.

show abstract

Section: De Novo Targeting In Homeostasis and Replication: I...mentioning

confidence: 99%

De Novo Polycomb Recruitment and Repressive Domain Formation

Hernández-Romero

Valdés

2022

Epigenomes

View full text Add to dashboard Cite

show abstract

“…Interestingly, mammalian CBX chromodomains can bind to DNA as well as H3K27me3. 72 , 73 , 74 Similarly, the C terminus of JARID2 has been reported to have affinity for DNA. 75 While the exact mechanism of JARID2-dependent CBX7 recruitment is still unclear, a recent cross-linked IP mass spectrometry experiment suggested JARID2 and CBX7 are in close proximity at target sites.…”

Section: Discussionmentioning

confidence: 98%

PRC2.1- and PRC2.2-specific accessory proteins drive recruitment of different forms of canonical PRC1

et al. 2023

View full text Add to dashboard Cite

“…In light of the functional significance of CBX8 in inducing malignancy in multiple cancer types, it has been suggested as a therapeutic target for cancer treatment and very recently its inhibitors have been developed and are being tested [ 35 , 52 , 53 ]. Our study showed that patients with high NAT CBX8 were associated with a worse stage, tumor invasion, lymph node metastasis, distant metastasis, and poor DFS and OS, suggesting that CRC patients with high NAT CBX8 are potential candidates for CBX8-targeted treatment.…”

Section: Discussionmentioning

confidence: 99%

High Expression of a Cancer Stemness-Related Gene, Chromobox 8 (CBX8), in Normal Tissue Adjacent to the Tumor (NAT) Is Associated with Poor Prognosis of Colorectal Cancer Patients

Ng¹,

Li²,

Man³

et al. 2022

Cells

View full text Add to dashboard Cite

Background: Several studies have demonstrated that the molecular profile of normal tissue adjacent to the tumor (NAT) is prognostic for recurrence in patients with different cancers. This study investigated the clinical significance of CBX8 gene expression, a cancer stemness-related gene, in tumor and NAT tissue of colorectal cancer (CRC) patients. Methods: The gene level of CBX8 in paired CRC and NAT specimens from 95 patients was determined by quantitative PCR. CBX8 protein level in CRC and NAT specimens from 66 patients was determined by immunohistochemistry. CBX8 gene and protein levels were correlated with the patients’ clinicopathological parameters and circulatory immune cell profiles. The association between CBX8 and pluripotency-associated genes was analyzed using the TCGA database. Results: NAT CBX8 gene level positively correlated with TNM stage, tumor invasion, lymph node metastasis and distant metastasis, indicating its association with tumor progression and metastasis. There was no correlation between NAT CBX8 protein level and clinicopathological parameters. Moreover, a high level of CBX8 gene and protein in NAT both correlated with poor DFS and OS. There was an inverse correlation between CBX8 gene level and post-operative platelet counts and platelet to lymphocyte level, suggesting its association with systematic inflammation. Finally, TCGA analysis showed that CBX8 level was correlated with a couple of pluripotency-associated genes, supporting its association with cancer stemness. Conclusions: High NAT CBX8 is a poor prognostic factor for tumor progression and survival in CRC patients.

show abstract

Reprogramming CBX8-PRC1 function with a positive allosteric modulator

Cited by 15 publications

References 88 publications

De Novo Polycomb Recruitment and Repressive Domain Formation

De Novo Polycomb Recruitment and Repressive Domain Formation

PRC2.1- and PRC2.2-specific accessory proteins drive recruitment of different forms of canonical PRC1

High Expression of a Cancer Stemness-Related Gene, Chromobox 8 (CBX8), in Normal Tissue Adjacent to the Tumor (NAT) Is Associated with Poor Prognosis of Colorectal Cancer Patients

Contact Info

Product

Resources

About