Altering chromatin methylation patterns and the transcriptional network involved in regulation of hematopoietic stem cell fate

doi:10.1002/jcp.29642

Review

. 2020 Oct;235(10):6404-6423.

doi: 10.1002/jcp.29642. Epub 2020 Feb 13.

Altering chromatin methylation patterns and the transcriptional network involved in regulation of hematopoietic stem cell fate

Mohammad Shokouhian¹, Marziye Bagheri², Behzad Poopak³, Rouzbeh Chegeni⁴, Nader Davari², Najmaldin Saki²

Affiliations

¹ Department of Hematology and Blood Transfusion, School of Allied Medical Sciences, Iran University of Medical Sciences, Tehran, Iran.
² Thalassemia and Hemoglobinopathy Research Center, Health Research Institute, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran.
³ Department of Hematology, Faculty of Paramedical Sciences, Tehran Medical Sciences, Islamic Azad University, Tehran, Iran.
⁴ Michener Institute of Education at University Health Network, Toronto, Canada.

PMID: 32052445
DOI: 10.1002/jcp.29642

Review

Altering chromatin methylation patterns and the transcriptional network involved in regulation of hematopoietic stem cell fate

Mohammad Shokouhian et al. J Cell Physiol. 2020 Oct.

. 2020 Oct;235(10):6404-6423.

doi: 10.1002/jcp.29642. Epub 2020 Feb 13.

Authors

Mohammad Shokouhian¹, Marziye Bagheri², Behzad Poopak³, Rouzbeh Chegeni⁴, Nader Davari², Najmaldin Saki²

Affiliations

¹ Department of Hematology and Blood Transfusion, School of Allied Medical Sciences, Iran University of Medical Sciences, Tehran, Iran.
² Thalassemia and Hemoglobinopathy Research Center, Health Research Institute, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran.
³ Department of Hematology, Faculty of Paramedical Sciences, Tehran Medical Sciences, Islamic Azad University, Tehran, Iran.
⁴ Michener Institute of Education at University Health Network, Toronto, Canada.

PMID: 32052445
DOI: 10.1002/jcp.29642

Abstract

Hematopoietic stem cells (HSCs) are quiescent cells with self-renewal capacity and potential multilineage development. Various molecular regulatory mechanisms such as epigenetic modifications and transcription factor (TF) networks play crucial roles in establishing a balance between self-renewal and differentiation of HSCs. Histone/DNA methylations are important epigenetic modifications involved in transcriptional regulation of specific lineage HSCs via controlling chromatin structure and accessibility of DNA. Also, TFs contribute to either facilitation or inhibition of gene expression through binding to enhancer or promoter regions of DNA. As a result, epigenetic factors and TFs regulate the activation or repression of HSCs genes, playing a central role in normal hematopoiesis. Given the importance of histone/DNA methylation and TFs in gene expression regulation, their aberrations, including changes in HSCs-related methylation of histone/DNA and TFs (e.g., CCAAT-enhancer-binding protein α, phosphatase and tensin homolog deleted on the chromosome 10, Runt-related transcription factor 1, signal transducers and activators of transcription, and RAS family proteins) could disrupt HSCs fate. Herewith, we summarize how dysregulations in the expression of genes related to self-renewal, proliferation, and differentiation of HSCs caused by changes in epigenetic modifications and transcriptional networks lead to clonal expansion and leukemic transformation.

Keywords: epigenetic modifications; gene expression; hematopoietic stem cells; leukemia; transcriptional regulation.

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References

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1. Abdel-Wahab, O., Gao, J., Adli, M., Dey, A., Trimarchi, T., Chung, Y. R., … Levine, R. L. (2013). Deletion of Asxl1 results in myelodysplasia and severe developmental defects in vivo. Journal of Experimental Medicine, 210(12), 2641-2659. https://doi.org/10.1084/jem.20131141
1. An, J., Gonzalez-Avalos, E., Chawla, A., Jeong, M., Lopez-Moyado, I. F., Li, W., … Rao, A. (2015). Acute loss of TET function results in aggressive myeloid cancer in mice. Nature Communications, 6, 10071. https://doi.org/10.1038/ncomms10071
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[1] Abdel-Wahab, O., Adli, M., LaFave, L. M., Gao, J., Hricik, T., Shih, A. H., … Levine, R. L. (2012). ASXL1 mutations promote myeloid transformation through loss of PRC2-mediated gene repression. Cancer Cell, 22(2), 180-193. https://doi.org/10.1016/j.ccr.2012.06.032

[2] Abdel-Wahab, O., Adli, M., LaFave, L. M., Gao, J., Hricik, T., Shih, A. H., … Levine, R. L. (2012). ASXL1 mutations promote myeloid transformation through loss of PRC2-mediated gene repression. Cancer Cell, 22(2), 180-193. https://doi.org/10.1016/j.ccr.2012.06.032

[3] Abdel-Wahab, O., Gao, J., Adli, M., Dey, A., Trimarchi, T., Chung, Y. R., … Levine, R. L. (2013). Deletion of Asxl1 results in myelodysplasia and severe developmental defects in vivo. Journal of Experimental Medicine, 210(12), 2641-2659. https://doi.org/10.1084/jem.20131141

[4] Abdel-Wahab, O., Gao, J., Adli, M., Dey, A., Trimarchi, T., Chung, Y. R., … Levine, R. L. (2013). Deletion of Asxl1 results in myelodysplasia and severe developmental defects in vivo. Journal of Experimental Medicine, 210(12), 2641-2659. https://doi.org/10.1084/jem.20131141

[5] An, J., Gonzalez-Avalos, E., Chawla, A., Jeong, M., Lopez-Moyado, I. F., Li, W., … Rao, A. (2015). Acute loss of TET function results in aggressive myeloid cancer in mice. Nature Communications, 6, 10071. https://doi.org/10.1038/ncomms10071

[6] An, J., Gonzalez-Avalos, E., Chawla, A., Jeong, M., Lopez-Moyado, I. F., Li, W., … Rao, A. (2015). Acute loss of TET function results in aggressive myeloid cancer in mice. Nature Communications, 6, 10071. https://doi.org/10.1038/ncomms10071

[7] Artinger, E. L., Mishra, B. P., Zaffuto, K. M., Li, B. E., Chung, E. K., Moore, A. W., … Ernst, P. (2013). An MLL-dependent network sustains hematopoiesis. Proceedings of the National Academy of Sciences of the United States of America, 110(29), 12000-12005. https://doi.org/10.1073/pnas.1301278110

[8] Artinger, E. L., Mishra, B. P., Zaffuto, K. M., Li, B. E., Chung, E. K., Moore, A. W., … Ernst, P. (2013). An MLL-dependent network sustains hematopoiesis. Proceedings of the National Academy of Sciences of the United States of America, 110(29), 12000-12005. https://doi.org/10.1073/pnas.1301278110

[9] Asada, S., Fujino, T., Goyama, S., & Kitamura, T. (2019). The role of ASXL1 in hematopoiesis and myeloid malignancies. Cellular and Molecular Life Sciences, 76(13), 2511-2523. https://doi.org/10.1007/s00018-019-03084-7

[10] Asada, S., Fujino, T., Goyama, S., & Kitamura, T. (2019). The role of ASXL1 in hematopoiesis and myeloid malignancies. Cellular and Molecular Life Sciences, 76(13), 2511-2523. https://doi.org/10.1007/s00018-019-03084-7

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Altering chromatin methylation patterns and the transcriptional network involved in regulation of hematopoietic stem cell fate

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Altering chromatin methylation patterns and the transcriptional network involved in regulation of hematopoietic stem cell fate

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