Cargando…
Eomes partners with PU.1 and MITF to Regulate Transcription Factors Critical for osteoclast differentiation
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 immunoprecip...
Autores principales: | , , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Elsevier
2018
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6327072/ https://www.ncbi.nlm.nih.gov/pubmed/30634169 http://dx.doi.org/10.1016/j.isci.2018.12.018 |
_version_ | 1783386403563896832 |
---|---|
author | Carey, Heather A. Hildreth, Blake E. Samuvel, Devadoss J. Thies, Katie A. Rosol, Thomas J. Toribio, Ramiro E. Charles, Julia F. Ostrowski, Michael C. Sharma, Sudarshana M. |
author_facet | Carey, Heather A. Hildreth, Blake E. Samuvel, Devadoss J. Thies, Katie A. Rosol, Thomas J. Toribio, Ramiro E. Charles, Julia F. Ostrowski, Michael C. Sharma, Sudarshana M. |
author_sort | Carey, Heather A. |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-6327072 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | Elsevier |
record_format | MEDLINE/PubMed |
spelling | pubmed-63270722019-01-22 Eomes partners with PU.1 and MITF to Regulate Transcription Factors Critical for osteoclast differentiation Carey, Heather A. Hildreth, Blake E. Samuvel, Devadoss J. Thies, Katie A. Rosol, Thomas J. Toribio, Ramiro E. Charles, Julia F. Ostrowski, Michael C. Sharma, Sudarshana M. iScience Article 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. Elsevier 2018-12-27 /pmc/articles/PMC6327072/ /pubmed/30634169 http://dx.doi.org/10.1016/j.isci.2018.12.018 Text en © 2019 Medical University of South Carolina http://creativecommons.org/licenses/by-nc-nd/4.0/ This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). |
spellingShingle | Article Carey, Heather A. Hildreth, Blake E. Samuvel, Devadoss J. Thies, Katie A. Rosol, Thomas J. Toribio, Ramiro E. Charles, Julia F. Ostrowski, Michael C. Sharma, Sudarshana M. Eomes partners with PU.1 and MITF to Regulate Transcription Factors Critical for osteoclast differentiation |
title | Eomes partners with PU.1 and MITF to Regulate Transcription Factors Critical for osteoclast differentiation |
title_full | Eomes partners with PU.1 and MITF to Regulate Transcription Factors Critical for osteoclast differentiation |
title_fullStr | Eomes partners with PU.1 and MITF to Regulate Transcription Factors Critical for osteoclast differentiation |
title_full_unstemmed | Eomes partners with PU.1 and MITF to Regulate Transcription Factors Critical for osteoclast differentiation |
title_short | Eomes partners with PU.1 and MITF to Regulate Transcription Factors Critical for osteoclast differentiation |
title_sort | eomes partners with pu.1 and mitf to regulate transcription factors critical for osteoclast differentiation |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6327072/ https://www.ncbi.nlm.nih.gov/pubmed/30634169 http://dx.doi.org/10.1016/j.isci.2018.12.018 |
work_keys_str_mv | AT careyheathera eomespartnerswithpu1andmitftoregulatetranscriptionfactorscriticalforosteoclastdifferentiation AT hildrethblakee eomespartnerswithpu1andmitftoregulatetranscriptionfactorscriticalforosteoclastdifferentiation AT samuveldevadossj eomespartnerswithpu1andmitftoregulatetranscriptionfactorscriticalforosteoclastdifferentiation AT thieskatiea eomespartnerswithpu1andmitftoregulatetranscriptionfactorscriticalforosteoclastdifferentiation AT rosolthomasj eomespartnerswithpu1andmitftoregulatetranscriptionfactorscriticalforosteoclastdifferentiation AT toribioramiroe eomespartnerswithpu1andmitftoregulatetranscriptionfactorscriticalforosteoclastdifferentiation AT charlesjuliaf eomespartnerswithpu1andmitftoregulatetranscriptionfactorscriticalforosteoclastdifferentiation AT ostrowskimichaelc eomespartnerswithpu1andmitftoregulatetranscriptionfactorscriticalforosteoclastdifferentiation AT sharmasudarshanam eomespartnerswithpu1andmitftoregulatetranscriptionfactorscriticalforosteoclastdifferentiation |