Gene expression is tightly linked to histone acetylation on lysine residues that can be recognized by bromodomains. The testis-specific bromodomain protein tBRD-1 is essential for male fertility and might act as a co-factor of testis-specifc TAFs. Here, we perform microarray analyses and demonstrate that tBRD-1 selectively controls gene expression in male germ cells
tBRD-1 selectively controls gene activity in the Drosophila testis and interacts with two new members of the bromodomain and extra-terminal (BET) family.
Specimen part
View SamplesWe here show that the niche regulates the quality of the hematopoietic stem cells (HSCs) that are regenerated after transplantation. We find that a reduced level of Wnt5a in the niche regenerates dysfunctional HSCs, which do not successfully engraft secondary recipients. In particular, RNA sequencing shows a dysregulated Zeb1-associated gene expression of multiple genes involved in the small GTPase-dependent actin polymerization pathway. Misexpression of these genes results in reduced ability to direct polarized F-actin localization, leading to defects in adhesion, migratory behavior and homing to the bone marrow of secondary recipients. Our study further shows that the Wnt5a-haploinsufficient environment similarly affects BCR-ABLp185+ cells, which, in 42% of the studied recipients, fail to generate leukemia and, in the remaining cases, fail to transfer leukemia to secondary hosts. Thus, we show that Wnt5a in the niche is required to regenerate HSCs and leukemic cells with functional ability to rearrange the actin cytoskeleton which is required for successful engraftment. Overall design: Hematopoietic stem cells are regenerated in WT or Wnt5a-haploinsufficient niches. We profile LSK hematopoiteic stem cells after transplantation and three cell populations from the niche environment: endothelial cells (EC), osteoblastic cells (OBC), and mesenchymal cells (MSC)
Niche WNT5A regulates the actin cytoskeleton during regeneration of hematopoietic stem cells.
Cell line, Subject
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