The T-Cell Oncogene Tal2 Is a Target of PU.1 and Upregulated during Osteoclastogenesis

Abstract

Transcription factors play a crucial role in regulating differentiation processes during human life and are important in disease. The basic helix-loop-helix transcription factors Tal1 and Lyl1 play a major role in the regulation of gene expression in the hematopoietic system and are involved in human leukemia. Tal2, which belongs to the same family of transcription factors as Tal1 and Lyl1, is also involved in human leukaemia. However, little is known regarding the expression and regulation of Tal2 in hematopoietic cells. Here we show that Tal2 is expressed in hematopoietic cells of the myeloid lineage. Interestingly, we found that usage of the Tal2 promoter is different in human and mouse cells. Two promoters, hP1 and hP2 drive Tal2 expression in human erythroleukemia K562 cells, however in mouse RAW cells only the mP1 promoter is used. Furthermore, we found that Tal2 expression is upregulated during oesteoclastogenesis. We show that Tal2 is a direct target gene of the myeloid transcription factor PU.1, which is a key transcription factor for osteoclast gene expression. Strikingly, PU.1 binding to the P1 promoter is conserved between mouse and human, but PU.1 binding to P2 was only detected in human K562 cells. Additionally, we provide evidence that Tal2 influences the expression of the osteoclastic differentiation gene TRACP. These findings provide novel insight into the expression control of Tal2 in hematopoietic cells and reveal a function of Tal2 as a regulator of gene expression during osteoclast differentiation.

Epigenetics of Skeletal Muscle-Associated Genes in the ASB, LRRC, TMEM, and OSBPL Gene Families

“…Both TMEM38A , highly specific for SkM, and the related TMEM38B , preferentially expressed in SkM but less specific for this tissue, have five exons, but with large differences in intron patterning that are reflected in different distributions of SkM enhancer chromatin at these genes ( Figure 5 b,d). The upstream neighbor of TMEM38B is the 0.7 kb intron-less TAL2 gene, which encodes an oncogenic TF essential for normal brain development in mice and implicated in osteoclastogenesis [ 46 , 47 ]. Although TAL2 has not been described as being related to SkM, we found that the highest (albeit low) steady-state levels of its RNA among the 53 studied tissues were in SkM (TPM, 0.7) and testis (TPM, 0.9; Table S4b and Figure S9 ).…”

Epigenetics of skeletal muscle-associated genes in theASB, LRRC, TMEM, andOSBPLgene families

“…Both TMEM38A , highly specific for SkM, and the related TMEM38B , preferentially expressed in SkM but less specific for this tissue, have five exons, but with large differences in intron patterning that are reflected in different distributions of SkM enhancer chromatin at these genes (Figure 5b and d). The upstream neighbor of TMEM38B is the 0.7-kb intron-less TAL2 gene, which encodes an oncogenic TF essential for normal brain development in mice and implicated in osteoclastogenesis [46, 47]. Although TAL2 has not been described as related to SkM, we found that the highest (albeit low) steady-state levels of its RNA among the 53 studied tissues were in SkM (TPM, 0.7) and testis (TPM, 0.9; Table S4b and Figure S4).…”

XL-DNase-seq: improved footprinting of dynamic transcription factors

“…In addition, well-known regulatory targets of RelA/NF-κB such as Nfkbia (a negative feedback gene), Rel (an immune-specific subunit of NF-κB), and Nfkb2 (an alternative dimer subunit of NF-κB) were robustly detected. RelA was also a putative regulator of Tfe3 (involved in macrophage autophagy and cytokine response, also detected as a putative target of PU.1 in multiple networks) [25] and Tal2 (a known target of PU.1) [6]. These regulatory connections were based on footprints detectable in both native and XL-DNase-seq data.…”