Abstract
Alterations in normal regulation of gene expression is one of the key features of hematopoietic malignancies. In order to gain insight into the mechanisms that regulate gene expression in these diseases, we dissected the role of the Ikaros protein in leukemia. Ikaros is a DNA-binding, zinc finger protein that functions as a transcriptional regulator and a tumor suppressor in leukemia. The use of ChIP-seq, RNA-seq, and ATAC-seq—coupled with functional experiments—revealed that Ikaros regulates both the global epigenomic landscape and epigenetic signature at promoter regions of its target genes. Casein kinase II (CK2), an oncogenic kinase that is overexpressed in leukemia, directly phosphorylates Ikaros at multiple, evolutionarily-conserved residues. Phosphorylation of Ikaros impairs the protein's ability to regulate both the transcription of its target genes and global epigenetic landscape in leukemia. Treatment of leukemia cells with a specific inhibitor of CK2 restores Ikaros function, resulting in cytotoxicity of leukemia cells. Here, we review the mechanisms through which the CK2-Ikaros signaling axis regulates the global epigenomic landscape and expression of genes that control cellular proliferation in leukemia.
| Original language | English (US) |
|---|---|
| Article number | 100665 |
| Journal | Advances in Biological Regulation |
| DOIs | |
| State | Accepted/In press - Jan 1 2019 |
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All Science Journal Classification (ASJC) codes
- Molecular Medicine
- Molecular Biology
- Genetics
- Cancer Research
Cite this
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Cellular signaling and epigenetic regulation of gene expression in leukemia. / Gowda, Chandrika; Song, Chunhua; Ding, Yali; Iyer, Soumya; Dhanyamraju, Pavan; McGrath, Mary; Bamme, Yevgeniya; Soliman, Mario; Kane, Shriya; Payne, Jonathon L.; Dovat, Sinisa.
In: Advances in Biological Regulation, 01.01.2019.Research output: Contribution to journal › Review article
TY - JOUR
T1 - Cellular signaling and epigenetic regulation of gene expression in leukemia
AU - Gowda, Chandrika
AU - Song, Chunhua
AU - Ding, Yali
AU - Iyer, Soumya
AU - Dhanyamraju, Pavan
AU - McGrath, Mary
AU - Bamme, Yevgeniya
AU - Soliman, Mario
AU - Kane, Shriya
AU - Payne, Jonathon L.
AU - Dovat, Sinisa
PY - 2019/1/1
Y1 - 2019/1/1
N2 - Alterations in normal regulation of gene expression is one of the key features of hematopoietic malignancies. In order to gain insight into the mechanisms that regulate gene expression in these diseases, we dissected the role of the Ikaros protein in leukemia. Ikaros is a DNA-binding, zinc finger protein that functions as a transcriptional regulator and a tumor suppressor in leukemia. The use of ChIP-seq, RNA-seq, and ATAC-seq—coupled with functional experiments—revealed that Ikaros regulates both the global epigenomic landscape and epigenetic signature at promoter regions of its target genes. Casein kinase II (CK2), an oncogenic kinase that is overexpressed in leukemia, directly phosphorylates Ikaros at multiple, evolutionarily-conserved residues. Phosphorylation of Ikaros impairs the protein's ability to regulate both the transcription of its target genes and global epigenetic landscape in leukemia. Treatment of leukemia cells with a specific inhibitor of CK2 restores Ikaros function, resulting in cytotoxicity of leukemia cells. Here, we review the mechanisms through which the CK2-Ikaros signaling axis regulates the global epigenomic landscape and expression of genes that control cellular proliferation in leukemia.
AB - Alterations in normal regulation of gene expression is one of the key features of hematopoietic malignancies. In order to gain insight into the mechanisms that regulate gene expression in these diseases, we dissected the role of the Ikaros protein in leukemia. Ikaros is a DNA-binding, zinc finger protein that functions as a transcriptional regulator and a tumor suppressor in leukemia. The use of ChIP-seq, RNA-seq, and ATAC-seq—coupled with functional experiments—revealed that Ikaros regulates both the global epigenomic landscape and epigenetic signature at promoter regions of its target genes. Casein kinase II (CK2), an oncogenic kinase that is overexpressed in leukemia, directly phosphorylates Ikaros at multiple, evolutionarily-conserved residues. Phosphorylation of Ikaros impairs the protein's ability to regulate both the transcription of its target genes and global epigenetic landscape in leukemia. Treatment of leukemia cells with a specific inhibitor of CK2 restores Ikaros function, resulting in cytotoxicity of leukemia cells. Here, we review the mechanisms through which the CK2-Ikaros signaling axis regulates the global epigenomic landscape and expression of genes that control cellular proliferation in leukemia.
UR - http://www.scopus.com/inward/record.url?scp=85073545516&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85073545516&partnerID=8YFLogxK
U2 - 10.1016/j.jbior.2019.100665
DO - 10.1016/j.jbior.2019.100665
M3 - Review article
C2 - 31623972
AN - SCOPUS:85073545516
JO - Advances in Biological Regulation
JF - Advances in Biological Regulation
SN - 2212-4926
M1 - 100665
ER -