Eos, MITF, and PU.1 recruit corepressors to osteoclast-specific genes in committed myeloid progenitors

Rong Hu, Sudarshana M. Sharma, Agnieszka Bronisz, Ruchika Srinivasan, Uma Sankar, Michael C. Ostrowski

Research output: Contribution to journalArticle

60 Citations (Scopus)

Abstract

Transcription factors MITF and PU.1 collaborate to increase expression of target genes like cathepsin K (Ctsk) and acid phosphatase 5 (Acp5) during osteoclast differentiation. We show that these factors can also repress transcription of target genes in committed myeloid precursors capable of forming either macrophages or osteoclasts. The direct interaction of MITF and PU.1 with the zinc finger protein Eos, an Ikaros family member, was necessary for repression of Ctsk and Acp5. Eos formed a complex with MITF and PU.1 at target gene promoters and suppressed transcription through recruitment of corepressors CtBP (C-terminal binding protein) and Sin3A, but during osteoclast differentiation, Eos association with Ctsk and Acp5 promoters was significantly decreased. Subsequently, MITF and PU.1 recruited coactivators to these target genes, resulting in robust expression of target genes. Overexpression of Eos in bone marrow-derived precursors disrupted osteoclast differentiation and selectively repressed transcription of MITF/PU.1 targets, while small interfering RNA knockdown of Eos resulted in increased basal expression of Ctsk and Acp5. This work provides a mechanism to account for the modulation of MITF and PU.1 activity in committed myeloid progenitors prior to the initiation of osteoclast differentiation in response to the appropriate extracellular signals.

Original languageEnglish (US)
Pages (from-to)4018-4027
Number of pages10
JournalMolecular and Cellular Biology
Volume27
Issue number11
DOIs
StatePublished - Jun 2007
Externally publishedYes

Fingerprint

Co-Repressor Proteins
Cathepsin K
Osteoclasts
Acid Phosphatase
Genes
Gene Expression
Zinc Fingers
Small Interfering RNA
Bone Marrow
Macrophages
Proteins

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Cell Biology

Cite this

Eos, MITF, and PU.1 recruit corepressors to osteoclast-specific genes in committed myeloid progenitors. / Hu, Rong; Sharma, Sudarshana M.; Bronisz, Agnieszka; Srinivasan, Ruchika; Sankar, Uma; Ostrowski, Michael C.

In: Molecular and Cellular Biology, Vol. 27, No. 11, 06.2007, p. 4018-4027.

Research output: Contribution to journalArticle

Hu, Rong ; Sharma, Sudarshana M. ; Bronisz, Agnieszka ; Srinivasan, Ruchika ; Sankar, Uma ; Ostrowski, Michael C. / Eos, MITF, and PU.1 recruit corepressors to osteoclast-specific genes in committed myeloid progenitors. In: Molecular and Cellular Biology. 2007 ; Vol. 27, No. 11. pp. 4018-4027.
@article{a11bab13b63e4a279046e0c6c1f75659,
title = "Eos, MITF, and PU.1 recruit corepressors to osteoclast-specific genes in committed myeloid progenitors",
abstract = "Transcription factors MITF and PU.1 collaborate to increase expression of target genes like cathepsin K (Ctsk) and acid phosphatase 5 (Acp5) during osteoclast differentiation. We show that these factors can also repress transcription of target genes in committed myeloid precursors capable of forming either macrophages or osteoclasts. The direct interaction of MITF and PU.1 with the zinc finger protein Eos, an Ikaros family member, was necessary for repression of Ctsk and Acp5. Eos formed a complex with MITF and PU.1 at target gene promoters and suppressed transcription through recruitment of corepressors CtBP (C-terminal binding protein) and Sin3A, but during osteoclast differentiation, Eos association with Ctsk and Acp5 promoters was significantly decreased. Subsequently, MITF and PU.1 recruited coactivators to these target genes, resulting in robust expression of target genes. Overexpression of Eos in bone marrow-derived precursors disrupted osteoclast differentiation and selectively repressed transcription of MITF/PU.1 targets, while small interfering RNA knockdown of Eos resulted in increased basal expression of Ctsk and Acp5. This work provides a mechanism to account for the modulation of MITF and PU.1 activity in committed myeloid progenitors prior to the initiation of osteoclast differentiation in response to the appropriate extracellular signals.",
author = "Rong Hu and Sharma, {Sudarshana M.} and Agnieszka Bronisz and Ruchika Srinivasan and Uma Sankar and Ostrowski, {Michael C.}",
year = "2007",
month = "6",
doi = "10.1128/MCB.01839-06",
language = "English (US)",
volume = "27",
pages = "4018--4027",
journal = "Molecular and Cellular Biology",
issn = "0270-7306",
publisher = "American Society for Microbiology",
number = "11",

}

TY - JOUR

T1 - Eos, MITF, and PU.1 recruit corepressors to osteoclast-specific genes in committed myeloid progenitors

AU - Hu, Rong

AU - Sharma, Sudarshana M.

AU - Bronisz, Agnieszka

AU - Srinivasan, Ruchika

AU - Sankar, Uma

AU - Ostrowski, Michael C.

PY - 2007/6

Y1 - 2007/6

N2 - Transcription factors MITF and PU.1 collaborate to increase expression of target genes like cathepsin K (Ctsk) and acid phosphatase 5 (Acp5) during osteoclast differentiation. We show that these factors can also repress transcription of target genes in committed myeloid precursors capable of forming either macrophages or osteoclasts. The direct interaction of MITF and PU.1 with the zinc finger protein Eos, an Ikaros family member, was necessary for repression of Ctsk and Acp5. Eos formed a complex with MITF and PU.1 at target gene promoters and suppressed transcription through recruitment of corepressors CtBP (C-terminal binding protein) and Sin3A, but during osteoclast differentiation, Eos association with Ctsk and Acp5 promoters was significantly decreased. Subsequently, MITF and PU.1 recruited coactivators to these target genes, resulting in robust expression of target genes. Overexpression of Eos in bone marrow-derived precursors disrupted osteoclast differentiation and selectively repressed transcription of MITF/PU.1 targets, while small interfering RNA knockdown of Eos resulted in increased basal expression of Ctsk and Acp5. This work provides a mechanism to account for the modulation of MITF and PU.1 activity in committed myeloid progenitors prior to the initiation of osteoclast differentiation in response to the appropriate extracellular signals.

AB - Transcription factors MITF and PU.1 collaborate to increase expression of target genes like cathepsin K (Ctsk) and acid phosphatase 5 (Acp5) during osteoclast differentiation. We show that these factors can also repress transcription of target genes in committed myeloid precursors capable of forming either macrophages or osteoclasts. The direct interaction of MITF and PU.1 with the zinc finger protein Eos, an Ikaros family member, was necessary for repression of Ctsk and Acp5. Eos formed a complex with MITF and PU.1 at target gene promoters and suppressed transcription through recruitment of corepressors CtBP (C-terminal binding protein) and Sin3A, but during osteoclast differentiation, Eos association with Ctsk and Acp5 promoters was significantly decreased. Subsequently, MITF and PU.1 recruited coactivators to these target genes, resulting in robust expression of target genes. Overexpression of Eos in bone marrow-derived precursors disrupted osteoclast differentiation and selectively repressed transcription of MITF/PU.1 targets, while small interfering RNA knockdown of Eos resulted in increased basal expression of Ctsk and Acp5. This work provides a mechanism to account for the modulation of MITF and PU.1 activity in committed myeloid progenitors prior to the initiation of osteoclast differentiation in response to the appropriate extracellular signals.

UR - http://www.scopus.com/inward/record.url?scp=34347356549&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=34347356549&partnerID=8YFLogxK

U2 - 10.1128/MCB.01839-06

DO - 10.1128/MCB.01839-06

M3 - Article

C2 - 17403896

AN - SCOPUS:34347356549

VL - 27

SP - 4018

EP - 4027

JO - Molecular and Cellular Biology

JF - Molecular and Cellular Biology

SN - 0270-7306

IS - 11

ER -