The transcription factor TAL1 and miR-17-92 create a regulatory loop in hematopoiesis.
Erythroid Cells
/ cytology
Feedback, Physiological
Gene Expression Regulation
HEK293 Cells
Hematopoiesis
Humans
Jurkat Cells
K562 Cells
MicroRNAs
/ genetics
Protein Stability
RNA, Long Noncoding
T-Cell Acute Lymphocytic Leukemia Protein 1
/ chemistry
Transcription Factor 3
/ metabolism
Transcriptional Activation
Journal
Scientific reports
ISSN: 2045-2322
Titre abrégé: Sci Rep
Pays: England
ID NLM: 101563288
Informations de publication
Date de publication:
08 12 2020
08 12 2020
Historique:
received:
23
03
2020
accepted:
24
11
2020
entrez:
9
12
2020
pubmed:
10
12
2020
medline:
25
3
2021
Statut:
epublish
Résumé
A network of gene regulatory factors such as transcription factors and microRNAs establish and maintain gene expression patterns during hematopoiesis. In this network, transcription factors regulate each other and are involved in regulatory loops with microRNAs. The microRNA cluster miR-17-92 is located within the MIR17HG gene and encodes six mature microRNAs. It is important for hematopoietic differentiation and plays a central role in malignant disease. However, the transcription factors downstream of miR-17-92 are largely elusive and the transcriptional regulation of miR-17-92 is not fully understood. Here we show that miR-17-92 forms a regulatory loop with the transcription factor TAL1. The miR-17-92 cluster inhibits expression of TAL1 and indirectly leads to decreased stability of the TAL1 transcriptional complex. We found that TAL1 and its heterodimerization partner E47 regulate miR-17-92 transcriptionally. Furthermore, miR-17-92 negatively influences erythroid differentiation, a process that depends on gene activation by the TAL1 complex. Our data give example of how transcription factor activity is fine-tuned during normal hematopoiesis. We postulate that disturbance of the regulatory loop between TAL1 and the miR-17-92 cluster could be an important step in cancer development and progression.
Identifiants
pubmed: 33293632
doi: 10.1038/s41598-020-78629-z
pii: 10.1038/s41598-020-78629-z
pmc: PMC7722897
doi:
Substances chimiques
MIR17HG, human
0
MicroRNAs
0
RNA, Long Noncoding
0
T-Cell Acute Lymphocytic Leukemia Protein 1
0
Transcription Factor 3
0
TAL1 protein, human
135471-20-4
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
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