Browsing by Author "Schneider, Lucas"

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Open Access
Investigation of the interaction of PRMT6 and LEF1/β-catenin in hematopoiesis
(2021) Schneider, Lucas; Lausen, Jörn (Prof. Dr.)
Open Access
PRMT6 activates cyclin D1 expression in conjunction with the transcription factor LEF1
(2021) Schneider, Lucas; Herkt, Stefanie; Wang, Lei; Feld, Christine; Wesely, Josephine; Kuvardina, Olga N.; Meyer, Annekarin; Oellerich, Thomas; Häupl, Björn; Seifried, Erhard; Bonig, Halvard; Lausen, Joern
The establishment of cell type specific gene expression by transcription factors and their epigenetic cofactors is central for cell fate decisions. Protein arginine methyltransferase 6 (PRMT6) is an epigenetic regulator of gene expression mainly through methylating arginines at histone H3. This way it influences cellular differentiation and proliferation. PRMT6 lacks DNA-binding capability but is recruited by transcription factors to regulate gene expression. However, currently only a limited number of transcription factors have been identified, which facilitate recruitment of PRMT6 to key cell cycle related target genes. Here, we show that LEF1 contributes to the recruitment of PRMT6 to the central cell cycle regulator CCND1 (Cyclin D1). We identified LEF1 as an interaction partner of PRMT6. Knockdown of LEF1 or PRMT6 reduces CCND1 expression. This is in line with our observation that knockdown of PRMT6 increases the number of cells in G1 phase of the cell cycle and decreases proliferation. These results improve the understanding of PRMT6 activity in cell cycle regulation. We expect that these insights will foster the rational development and usage of specific PRMT6 inhibitors for cancer therapy.
Open Access
The transcription factor TAL1 and miR-17-92 create a regulatory loop in hematopoiesis
(2020) Meyer, Annekarin; Herkt, Stefanie; Kunze-Schumacher, Heike; Kohrs, Nicole; Ringleb, Julia; Schneider, Lucas; Kuvardina, Olga N.; Oellerich, Thomas; Häupl, Björn; Krueger, Andreas; Seifried, Erhard; Bonig, Halvard; Lausen, Joern
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.