CARD10, a CEBPE target involved in granulocytic differentiation
Pavithra Shyamsunder,
Haresh Sankar,
Anand Mayakonda,
Lin Han,
Hazimah Binte Mohd Nordin,
Teoh Weoi Woon,
Mahalakshmi Shanmugasundaram,
Pushkar Dakle,
Vikas Madan,
H. Phillip Koeffler
Affiliations
Pavithra Shyamsunder
Cancer Science Institute of Singapore, National University of Singapore, Singapore
Haresh Sankar
Cancer Science Institute of Singapore, National University of Singapore, Singapore
Anand Mayakonda
Cancer Science Institute of Singapore, National University of Singapore, Singapore
Lin Han
Cancer Science Institute of Singapore, National University of Singapore, Singapore;Department of Medicine, Yong Loo Lin School of Medicine, National University of Singapore
Hazimah Binte Mohd Nordin
Cancer Science Institute of Singapore, National University of Singapore, Singapore
Teoh Weoi Woon
Cancer Science Institute of Singapore, National University of Singapore, Singapore
Mahalakshmi Shanmugasundaram
Cancer Science Institute of Singapore, National University of Singapore, Singapore
Pushkar Dakle
Cancer Science Institute of Singapore, National University of Singapore, Singapore
Vikas Madan
Cancer Science Institute of Singapore, National University of Singapore, Singapore
H. Phillip Koeffler
Cancer Science Institute of Singapore, National University of Singapore, Singapore;Cedars-Sinai Medical Center, Division of Hematology/Oncology, UCLA School of Medicine, Los Angeles, CA, USA;Department of Hematology-Oncology, National University Cancer Institute of Singapore (NCIS), National University Hospital, Singapore
Maturation of granulocytes is dependent on controlled gene expression by myeloid lineage restricted transcription factors. CEBPE is one of the essential transcription factors required for granulocytic differentiation. Identification of downstream targets of CEBPE is vital to understand better its role in terminal granulopoiesis. In this study, we have identified Card10 as a novel target of CEBPE. We show that CEBPE binds to regulatory elements upstream of the murine Card10 locus, and expression of CARD10 is significantly reduced in Cebpe knock-out mice. Silencing Card10 in a human cell line and in murine primary cells impaired granulopoiesis, affecting expression of genes involved in myeloid cell development and function. Taken together, our data demonstrate for the first time that Card10 is expressed in granulocytes and is a direct target of CEBPE with functions extending to myeloid differentiation.
