Mll-COMPASS complexes mediate H3K4me3 enrichment and transcription of the osteoblast master gene Runx2/p57 in osteoblasts

Adriana Rojas, Hugo Sepulveda, Berta Henriquez, Rodrigo Aguilar, Tatiana Opazo, Gino Nardocci, Fernando Bustos, Jane B. Lian, Janet L. Stein, Gary S. Stein, Brigitte van Zundert, Andre J. van Wijnen, Miguel L. Allende, Martin Montecino

Research output: Contribution to journalArticle

1 Citation (Scopus)

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.

Original languageEnglish
JournalJournal of Cellular Physiology
DOIs
Publication statusAccepted/In press - 1 Jan 2018

Fingerprint

Osteoblasts
Transcription
Genes
Epigenomics
Core Binding Factor Alpha 1 Subunit
Histone Code
Proteins
Histones
Chromatin
Cells

Keywords

  • epigenetic control of osteoblast gene transcription
  • osteoblast differentiation
  • Runx2

ASJC Scopus subject areas

  • Physiology
  • Clinical Biochemistry
  • Cell Biology

Cite this

Rojas, Adriana ; Sepulveda, Hugo ; Henriquez, Berta ; Aguilar, Rodrigo ; Opazo, Tatiana ; Nardocci, Gino ; Bustos, Fernando ; Lian, Jane B. ; Stein, Janet L. ; Stein, Gary S. ; van Zundert, Brigitte ; van Wijnen, Andre J. ; Allende, Miguel L. ; Montecino, Martin. / Mll-COMPASS complexes mediate H3K4me3 enrichment and transcription of the osteoblast master gene Runx2/p57 in osteoblasts. In: Journal of Cellular Physiology. 2018.
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Mll-COMPASS complexes mediate H3K4me3 enrichment and transcription of the osteoblast master gene Runx2/p57 in osteoblasts. / Rojas, Adriana; Sepulveda, Hugo; Henriquez, Berta; Aguilar, Rodrigo; Opazo, Tatiana; Nardocci, Gino; Bustos, Fernando; Lian, Jane B.; Stein, Janet L.; Stein, Gary S.; van Zundert, Brigitte; van Wijnen, Andre J.; Allende, Miguel L.; Montecino, Martin.

In: Journal of Cellular Physiology, 01.01.2018.

Research output: Contribution to journalArticle

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T1 - Mll-COMPASS complexes mediate H3K4me3 enrichment and transcription of the osteoblast master gene Runx2/p57 in osteoblasts

AU - Rojas, Adriana

AU - Sepulveda, Hugo

AU - Henriquez, Berta

AU - Aguilar, Rodrigo

AU - Opazo, Tatiana

AU - Nardocci, Gino

AU - Bustos, Fernando

AU - Lian, Jane B.

AU - Stein, Janet L.

AU - Stein, Gary S.

AU - van Zundert, Brigitte

AU - van Wijnen, Andre J.

AU - Allende, Miguel L.

AU - Montecino, Martin

PY - 2018/1/1

Y1 - 2018/1/1

N2 - 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.

AB - 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.

KW - epigenetic control of osteoblast gene transcription

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