PUBLICATION
Dysregulation of NIPBL leads to impaired RUNX1 expression and haematopoietic defects
- Authors
- Mazzola, M., Pezzotta, A., Fazio, G., Rigamonti, A., Bresciani, E., Gaudenzi, G., Pelleri, M.C., Saitta, C., Ferrari, L., Parma, M., Fumagalli, M., Biondi, A., Cazzaniga, G., Marozzi, A., Pistocchi, A.
- ID
- ZDB-PUB-200424-6
- Date
- 2020
- Source
- Journal of Cellular and Molecular Medicine 24(11): 6272-6282 (Journal)
- Registered Authors
- Bresciani, Erica
- Keywords
- AML, NIPBL, RUNX1, haematopoiesis, zebrafish
- MeSH Terms
-
- Adult
- Aged
- Animals
- Bone Marrow Cells/metabolism
- Cell Cycle Proteins/genetics*
- Cell Cycle Proteins/metabolism
- Child
- Cohort Studies
- Core Binding Factor Alpha 2 Subunit/genetics*
- Core Binding Factor Alpha 2 Subunit/metabolism
- Down-Regulation/genetics
- Gene Expression Regulation, Leukemic*
- Hematopoiesis/genetics*
- Humans
- Leukemia, Myeloid, Acute/genetics
- Megakaryocytes/metabolism
- Middle Aged
- Tissue Donors
- Zebrafish/genetics
- Zebrafish Proteins/genetics*
- Zebrafish Proteins/metabolism
- PubMed
- 32323916 Full text @ J. Cell. Mol. Med.
Citation
Mazzola, M., Pezzotta, A., Fazio, G., Rigamonti, A., Bresciani, E., Gaudenzi, G., Pelleri, M.C., Saitta, C., Ferrari, L., Parma, M., Fumagalli, M., Biondi, A., Cazzaniga, G., Marozzi, A., Pistocchi, A. (2020) Dysregulation of NIPBL leads to impaired RUNX1 expression and haematopoietic defects. Journal of Cellular and Molecular Medicine. 24(11):6272-6282.
Abstract
The transcription factor RUNX1, a pivotal regulator of HSCs and haematopoiesis, is a frequent target of chromosomal translocations, point mutations or altered gene/protein dosage. These modifications lead or contribute to the development of myelodysplasia, leukaemia or platelet disorders. A better understanding of how regulatory elements contribute to fine-tune the RUNX1 expression in haematopoietic tissues could improve our knowledge of the mechanisms responsible for normal haematopoiesis and malignancy insurgence. The cohesin RAD21 was reported to be a regulator of RUNX1 expression in the human myeloid HL60 cell line and during primitive haematopoiesis in zebrafish. In our study, we demonstrate that another cohesin, NIPBL, exerts positive regulation of RUNX1 in three different contexts in which RUNX1 displays important functions: in megakaryocytes derived from healthy donors, in bone marrow samples obtained from adult patients with acute myeloid leukaemia and during zebrafish haematopoiesis. In this model, we demonstrate that alterations in the zebrafish orthologue nipblb reduce runx1 expression with consequent defects in its erythroid and myeloid targets such as gata1a and spi1b in an opposite way to rad21. Thus, also in the absence of RUNX1 translocation or mutations, additional factors such as defects in the expression of NIPBL might induce haematological diseases.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping