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Mll‐COMPASS complexes mediate H3K4me3 enrichment and transcription of the osteoblast master gene Runx2/p57 in osteoblasts
Author(s) -
Rojas Adriana,
Sepulveda Hugo,
Henriquez Berta,
Aguilar Rodrigo,
Opazo Tatiana,
Nardocci Gino,
Bustos Fernando,
Lian Jane B.,
Stein Janet L.,
Stein Gary S.,
Zundert Brigitte,
Wijnen Andre J.,
Allende Miguel L.,
Montecino Martin
Publication year - 2019
Publication title -
journal of cellular physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.529
H-Index - 174
eISSN - 1097-4652
pISSN - 0021-9541
DOI - 10.1002/jcp.27355
Subject(s) - runx2 , h3k4me3 , gene knockdown , transcription factor , promoter , osteoblast , biology , transcription (linguistics) , epigenetics , microbiology and biotechnology , chromatin immunoprecipitation , chromatin , mef2 , gene expression , gene , enhancer , genetics , linguistics , philosophy , in vitro
Abstract Expression of Runx2/p57 is a hallmark of the osteoblast‐lineage identity. Although several regulators that control the expression of Runx2/p57 during osteoblast‐lineage commitment have been identified, the epigenetic mechanisms that sustain this expression in differentiated osteoblasts remain to be completely determined. Here, we assess epigenetic mechanisms associated with Runx2/p57 gene transcription in differentiating MC3T3 mouse osteoblasts. Our results show that an enrichment of activating histone marks at the Runx2/p57 P1 promoter is accompanied by the simultaneous interaction of Wdr5 and Utx proteins, both are components of COMPASS complexes. Knockdown of Wdr5 and Utx expression confirms the activating role of both proteins at the Runx2‐P1 promoter. Other chromatin modifiers that were previously described to regulate Runx2/p57 transcription in mesenchymal precursor cells (Ezh2, Prmt5, and Jarid1b proteins) were not found to contribute to Runx2/p57 transcription in full‐committed osteoblasts. We also determined the presence of additional components of COMPASS complexes at the Runx2/p57 promoter, evidencing that the Mll2/COMPASS‐ and Mll3/COMPASS‐like complexes bind to the P1 promoter in osteoblastic cells expressing Runx2/p57 to modulate the H3K4me1 to H3K4me3 transition.