Abstract
Hematopoiesis is a complex process regulated by sets of transcription factors in a stage-specific and context-dependent manner. THAP11 is a transcription factor involved in cell growth, ES cell pluripotency, and embryogenesis. Here we showed that THAP11 was down-regulated during erythroid differentiation but up-regulated during megakaryocytic differentiation of cord blood CD34+ cells. Overexpression of THAP11 in K562 cells inhibited the erythroid differentiation induced by hemin with decreased numbers of benzidine-positive cells and decreased mRNA levels of α-globin (HBA) and glycophorin A (GPA), and knockdown of THAP11 enhanced the erythroid differentiation. Conversely, THAP11 overexpression accelerated the megakaryocytic differentiation induced by phorbol myristate acetate (PMA) with increased percentage of CD41+ cells, increased numbers of 4N cells, and elevated CD61 mRNA levels, and THAP11 knockdown attenuated the megakaryocytic differentiation. The expression levels of transcription factors such as c-Myc, c-Myb, GATA-2, and Fli1 were changed by THAP11 overexpression. In this way, our results suggested that THAP11 reversibly regulated erythroid and megakaryocytic differentiation.
Highlights
Hematopoietic stem cells (HSCs) differentiate to a number of divergent yet narrowly defined lineages, each giving rise to a specific type of blood cell
We show that THAP11 plays dual actions on erythroid differentiation and megakaryocytic differentiation
Using K562 cells as a model, we found that overexpression of THAP11 suppressed hemin induced erythroid differentiation of K562 cells with fewer benzidine-positive cells and lower mRNA levels of HBA and glycophorin A (GPA)
Summary
Hematopoietic stem cells (HSCs) differentiate to a number of divergent yet narrowly defined lineages, each giving rise to a specific type of blood cell. THAP proteins (.100 distinct members in the animal kingdom), a novel family of cellular factors, are defined by the presence of an evolutionarily conserved C2-CH (C-X2-4-C-X35-50C-X2-H) zinc finger motif of approximately 90 residues with sequence-specific DNA-binding activity [2]. This motif is called the THAP domain [3]. Ronin binds to HCF-1, a highly conserved enhancer element located at or immediately upstream of transcription start sites of a subset genes involved in transcription initiation, mRNA splicing, and cell metabolism [9] These studies suggest that THAP11 is a key transcriptional regulator involved in cell growth and differentiation
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
