The roles of Polycomb group proteins in hematopoietic stem cells and hematological malignancies

Takamatsu-Ichihara, Emi; Kitabayashi, Issay

doi:10.1007/s12185-016-2011-5

Cited by 27 publications

(32 citation statements)

References 96 publications

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“…PRC2 genes also play important roles in the regulation of hematopoiesis . Ezh2 overexpression in HSC enhanced their self‐renewal and prevented HSC exhaustion upon serial transplantation.…”

Section: Role Of Epigenetic Modifiers In Hematopoiesis: Lessons From mentioning

confidence: 99%

Epigenetics in normal and malignant hematopoiesis: An overview and update 2017

Goyama

Kitamura

2017

Cancer Science

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Epigenetic regulation in hematopoiesis has been a field of rapid expansion. Genome‐wide analyses have revealed, and will continue to identify genetic alterations in epigenetic genes that are present in various types of hematopoietic neoplasms. Development of new mouse models for individual epigenetic modifiers has revealed their novel, sometimes unexpected, functions. In this review, we provide an overview of genetic alterations within epigenetic genes in various types of hematopoietic neoplasms. We then summarize the physiologic roles of these epigenetic modifiers during hematopoiesis, and describe therapeutic approaches targeting the epigenetic modifications. Interestingly, the mutational spectrum of epigenetic genes indicates that myeloid neoplasms are similar to T‐cell neoplasms, whereas B‐cell lymphomas have distinct features. Furthermore, it appears that the epigenetic mutations related to active transcription are more associated with myeloid/T‐cell neoplasms, whereas those that repress transcription are associated with B‐cell lymphomas. These observations may imply that the global low‐level or high‐level transcriptional activity underlies the development of myeloid/T‐cell tumors or B‐cell tumors, respectively.

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Section: Role Of Epigenetic Modifiers In Hematopoiesis: Lessons From mentioning

confidence: 99%

Epigenetics in normal and malignant hematopoiesis: An overview and update 2017

Goyama

Kitamura

2017

Cancer Science

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“…As PcG proteins and miRNAs are usually co-expressed in many cell types or cancer tissues, such as keratinocytes (Eckert et al., 2011, Yi et al., 2008), hematopoietic stem cells (Takamatsu-Ichihara and Kitabayashi, 2016), hepatocellular carcinoma (Yonemitsu et al., 2009), lung cancer (Chen et al., 2015, Jin et al., 2013), breast cancer (Ru et al., 2011, Yu et al., 2012), and prostate cancer (Viticchie et al., 2011), it will be of interest to elucidate the complicated regulatory network involving multiple epigenetic factors that are responsible for determining cell fate and balancing the proliferation and differentiation of different cell types in future studies. The detailed regulatory network involving PcG proteins and other epigenetic factors that are responsible for altered NSPC behaviors will provide critical insights into the cellular control of NSPC proliferation and fate choices, and might lead us to find new therapeutic strategies for the treatment of neurological diseases.…”

Section: Discussionmentioning

confidence: 99%

“…Polycomb group (PcG) proteins comprise the Polycomb complexes PRC1 and PRC2 in the nucleus and regulate gene expression levels through histone modifications (Sparmann and van Lohuizen, 2006, Takamatsu-Ichihara and Kitabayashi, 2016). Dysregulation of PcG proteins can contribute to a number of human diseases, most notably cancer (Bracken and Helin, 2009, Margueron and Reinberg, 2011).…”

Section: Introductionmentioning

confidence: 99%

MiR-203 Interplays with Polycomb Repressive Complexes to Regulate the Proliferation of Neural Stem/Progenitor Cells

Tang

et al. 2017

Stem Cell Reports

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SummaryThe polycomb repressive complexes 1 (PRC1) and 2 (PRC2) are two distinct polycomb group (PcG) proteins that maintain the stable silencing of specific sets of genes through chromatin modifications. Although the PRC2 component EZH2 has been known as an epigenetic regulator in promoting the proliferation of neural stem/progenitor cells (NSPCs), the regulatory network that controls this process remains largely unknown. Here we show that miR-203 is repressed by EZH2 in both embryonic and adult NSPCs. MiR-203 negatively regulates the proliferation of NSPCs. One of PRC1 components, Bmi1, is a downstream target of miR-203 in NSPCs. Conditional knockout of Ezh2 results in decreased proliferation ability of both embryonic and adult NSPCs. Meanwhile, ectopic overexpression of BMI1 rescues the proliferation defects exhibited by miR-203 overexpression or EZH2 deficiency in NSPCs. Therefore, this study provides evidence for coordinated function of the EZH2-miR-203-BMI1 regulatory axis that regulates the proliferation of NSPCs.

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“…While canonical Ezh2 target genes were significantly de-repressed on deletion of Ezh2 in a mouse MDS model, a substantial portion of these genes became repressed again over time, suggesting a compensatory function for Ezh1 [6]. Given that Ezh1/ Ezh2 double knockout mice showed severely compromised function of HSCs, it appears that Ezh1 is essential for the maintenance of Ezh2-deficient HSCs [7,9].…”

Section: Ezh2mentioning

confidence: 97%

“…In addition to canonical PRC1, there are at least four PRC1 variants that also show monoubiquitylation activity at H2AK119 and which can function independently of PRC2 [4]. PRC2 is a critical regulator of normal hematopoiesis [5,6]. Loss of EED function profoundly compromises adult, but not fetal, hematopoiesis due to impaired repopulation and differentiation of hematopoietic stem cells (HSCs) in mice [7].…”

Section: Epigenetics In Hematological Malignanciesmentioning

confidence: 99%