Eomes partners with PU.1 and MITF to Regulate Transcription Factors Critical for osteoclast differentiation
Heather A. Carey,
Blake E. Hildreth, III,
Devadoss J. Samuvel,
Katie A. Thies,
Thomas J. Rosol,
Ramiro E. Toribio,
Julia F. Charles,
Michael C. Ostrowski,
Sudarshana M. Sharma
Affiliations
Heather A. Carey
Department of Cancer Biology and Genetics and Comprehensive Cancer Center, The Ohio State University Wexner Medical Center, Columbus, OH 43210, USA
Blake E. Hildreth, III
Department of Cancer Biology and Genetics and Comprehensive Cancer Center, The Ohio State University Wexner Medical Center, Columbus, OH 43210, USA; College of Veterinary Medicine, The Ohio State University, Columbus, OH 43210, USA; Department of Biochemistry and Molecular Biology and Hollings Cancer Center, Medical University of South Carolina, Hollings Cancer Center, 86 Jonathan Lucas St, Charleston, SC 29425, USA
Devadoss J. Samuvel
Department of Biochemistry and Molecular Biology and Hollings Cancer Center, Medical University of South Carolina, Hollings Cancer Center, 86 Jonathan Lucas St, Charleston, SC 29425, USA
Katie A. Thies
Department of Cancer Biology and Genetics and Comprehensive Cancer Center, The Ohio State University Wexner Medical Center, Columbus, OH 43210, USA; Department of Biochemistry and Molecular Biology and Hollings Cancer Center, Medical University of South Carolina, Hollings Cancer Center, 86 Jonathan Lucas St, Charleston, SC 29425, USA
Thomas J. Rosol
College of Veterinary Medicine, The Ohio State University, Columbus, OH 43210, USA; Department of Biomedical Sciences, Heritage College of Osteopathic Medicine, Ohio University, Athens, OH 45701, USA
Ramiro E. Toribio
College of Veterinary Medicine, The Ohio State University, Columbus, OH 43210, USA
Julia F. Charles
Department of Medicine, Division of Rheumatology, Immunology and Allergy, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA
Michael C. Ostrowski
Department of Cancer Biology and Genetics and Comprehensive Cancer Center, The Ohio State University Wexner Medical Center, Columbus, OH 43210, USA; Department of Biochemistry and Molecular Biology and Hollings Cancer Center, Medical University of South Carolina, Hollings Cancer Center, 86 Jonathan Lucas St, Charleston, SC 29425, USA; Corresponding author
Sudarshana M. Sharma
Department of Cancer Biology and Genetics and Comprehensive Cancer Center, The Ohio State University Wexner Medical Center, Columbus, OH 43210, USA; Department of Biochemistry and Molecular Biology and Hollings Cancer Center, Medical University of South Carolina, Hollings Cancer Center, 86 Jonathan Lucas St, Charleston, SC 29425, USA; Corresponding author
Summary: Bone-resorbing osteoclasts (OCs) are derived from myeloid precursors (MPs). Several transcription factors are implicated in OC differentiation and function; however, their hierarchical architecture and interplay are not well known. Analysis for enriched motifs in PU.1 and MITF chromatin immunoprecipitation coupled with high-throughput sequencing (ChIP-seq) data from differentiating OCs identified eomesodermin (EOMES) as a potential novel binding partner of PU.1 and MITF at genes critical for OC differentiation and function. We were able to demonstrate using co-immunoprecipitation and sequential ChIP analysis that PU.1, MITF, and EOMES are in the same complex and present as a complex at OC genomic loci. Furthermore, EOMES knockdown in MPs led to osteopetrosis associated with decreased OC differentiation and function both in vitro and in vivo. Although EOMES is associated with embryonic development and other hematopoietic lineages, this is the first study demonstrating the requirement of EOMES in the myeloid compartment. : Biological Sciences; Cell Biology; Developmental Biology; Omics Subject Areas: Biological Sciences, Cell Biology, Developmental Biology, Omics
