The Treacher Collins syndrome (TCOF1) gene product is involved in ribosomal DNA gene transcription by interacting with upstream binding factorCitation formats

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The Treacher Collins syndrome (TCOF1) gene product is involved in ribosomal DNA gene transcription by interacting with upstream binding factor. / Valdez, Benigno C.; Henning, Dale; So, Rolando B.; Dixon, Jill; Dixon, Michael J.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 101, No. 29, 20.07.2004, p. 10709-10714.

Research output: Contribution to journalArticle

Harvard

Valdez, BC, Henning, D, So, RB, Dixon, J & Dixon, MJ 2004, 'The Treacher Collins syndrome (TCOF1) gene product is involved in ribosomal DNA gene transcription by interacting with upstream binding factor', Proceedings of the National Academy of Sciences of the United States of America, vol. 101, no. 29, pp. 10709-10714. https://doi.org/10.1073/pnas.0402492101

APA

Valdez, B. C., Henning, D., So, R. B., Dixon, J., & Dixon, M. J. (2004). The Treacher Collins syndrome (TCOF1) gene product is involved in ribosomal DNA gene transcription by interacting with upstream binding factor. Proceedings of the National Academy of Sciences of the United States of America, 101(29), 10709-10714. https://doi.org/10.1073/pnas.0402492101

Vancouver

Valdez BC, Henning D, So RB, Dixon J, Dixon MJ. The Treacher Collins syndrome (TCOF1) gene product is involved in ribosomal DNA gene transcription by interacting with upstream binding factor. Proceedings of the National Academy of Sciences of the United States of America. 2004 Jul 20;101(29):10709-10714. https://doi.org/10.1073/pnas.0402492101

Author

Valdez, Benigno C. ; Henning, Dale ; So, Rolando B. ; Dixon, Jill ; Dixon, Michael J. / The Treacher Collins syndrome (TCOF1) gene product is involved in ribosomal DNA gene transcription by interacting with upstream binding factor. In: Proceedings of the National Academy of Sciences of the United States of America. 2004 ; Vol. 101, No. 29. pp. 10709-10714.

Bibtex

@article{fd8eee6e2cc74389bdbaf8510c570df9,
title = "The Treacher Collins syndrome (TCOF1) gene product is involved in ribosomal DNA gene transcription by interacting with upstream binding factor",
abstract = "Treacher Collins syndrome (TCS) is an autosomal dominant disorder characterized by an abnormality of craniofacial development that arises during early embryogenesis. TCS is caused by mutations in the gene TCOF1, which encodes the nucleolar phosphoprotein treacle. Even though the genetic alterations causing TCS have been uncovered, the mechanism underlying its pathogenesis and the function of treacle remain unknown. Here, we show that treacle is involved in ribosomal DNA gene transcription by interacting with upstream binding factor (UBF). Immunofluorescence labeling shows treacle and UBF colocalize to specific nucleolar organizer regions and cosegregate within nucleolar caps of actinomycin D-treated HeLa cells. Biochemical analysis shows the association of treacle and UBF with chromatin. Immunoprecipitation and the yeast two-hybrid system both suggest physical interaction of the two nucleolar phosphoproteins. Down-regulation of treacle expression using specific short interfering RNA results in inhibition of ribosomal DNA transcription and cell growth. A similar correlation is observed in Tcof+/- mouse embryos that exhibit craniofacial defects and growth retardation. Thus, treacle haploinsufficiency in TCS patients might result in abnormal development caused by inadequate ribosomal RNA production in the prefusion neural folds during the early stages of embryogenesis. The elucidation of a physiological function of treacle provides important information of relevance to the molecular dissection of the biochemical pathology of TCS.",
keywords = "Animals, physiology: Cell Cycle, metabolism: Chromatin, metabolism: DNA, Ribosomal, metabolism: Dactinomycin, Hela Cells, Human, Mice, genetics: Nuclear Proteins, metabolism: Nucleolus Organizer Region, genetics: Phosphoproteins, metabolism: Pol1 Transcription Initiation Complex Proteins, Protein Binding, genetics: RNA, Small Interfering, genetics: Recombinant Fusion Proteins, Support, Non-U.S. Gov't, Support, U.S. Gov't, P.H.S., Transcription, Genetic, Two-Hybrid System Techniques",
author = "Valdez, {Benigno C.} and Dale Henning and So, {Rolando B.} and Jill Dixon and Dixon, {Michael J.}",
year = "2004",
month = "7",
day = "20",
doi = "10.1073/pnas.0402492101",
language = "English",
volume = "101",
pages = "10709--10714",
journal = "Proceedings of the National Academy of Sciences",
issn = "0027-8424",
publisher = "National Academy of Sciences",
number = "29",

}

RIS

TY - JOUR

T1 - The Treacher Collins syndrome (TCOF1) gene product is involved in ribosomal DNA gene transcription by interacting with upstream binding factor

AU - Valdez, Benigno C.

AU - Henning, Dale

AU - So, Rolando B.

AU - Dixon, Jill

AU - Dixon, Michael J.

PY - 2004/7/20

Y1 - 2004/7/20

N2 - Treacher Collins syndrome (TCS) is an autosomal dominant disorder characterized by an abnormality of craniofacial development that arises during early embryogenesis. TCS is caused by mutations in the gene TCOF1, which encodes the nucleolar phosphoprotein treacle. Even though the genetic alterations causing TCS have been uncovered, the mechanism underlying its pathogenesis and the function of treacle remain unknown. Here, we show that treacle is involved in ribosomal DNA gene transcription by interacting with upstream binding factor (UBF). Immunofluorescence labeling shows treacle and UBF colocalize to specific nucleolar organizer regions and cosegregate within nucleolar caps of actinomycin D-treated HeLa cells. Biochemical analysis shows the association of treacle and UBF with chromatin. Immunoprecipitation and the yeast two-hybrid system both suggest physical interaction of the two nucleolar phosphoproteins. Down-regulation of treacle expression using specific short interfering RNA results in inhibition of ribosomal DNA transcription and cell growth. A similar correlation is observed in Tcof+/- mouse embryos that exhibit craniofacial defects and growth retardation. Thus, treacle haploinsufficiency in TCS patients might result in abnormal development caused by inadequate ribosomal RNA production in the prefusion neural folds during the early stages of embryogenesis. The elucidation of a physiological function of treacle provides important information of relevance to the molecular dissection of the biochemical pathology of TCS.

AB - Treacher Collins syndrome (TCS) is an autosomal dominant disorder characterized by an abnormality of craniofacial development that arises during early embryogenesis. TCS is caused by mutations in the gene TCOF1, which encodes the nucleolar phosphoprotein treacle. Even though the genetic alterations causing TCS have been uncovered, the mechanism underlying its pathogenesis and the function of treacle remain unknown. Here, we show that treacle is involved in ribosomal DNA gene transcription by interacting with upstream binding factor (UBF). Immunofluorescence labeling shows treacle and UBF colocalize to specific nucleolar organizer regions and cosegregate within nucleolar caps of actinomycin D-treated HeLa cells. Biochemical analysis shows the association of treacle and UBF with chromatin. Immunoprecipitation and the yeast two-hybrid system both suggest physical interaction of the two nucleolar phosphoproteins. Down-regulation of treacle expression using specific short interfering RNA results in inhibition of ribosomal DNA transcription and cell growth. A similar correlation is observed in Tcof+/- mouse embryos that exhibit craniofacial defects and growth retardation. Thus, treacle haploinsufficiency in TCS patients might result in abnormal development caused by inadequate ribosomal RNA production in the prefusion neural folds during the early stages of embryogenesis. The elucidation of a physiological function of treacle provides important information of relevance to the molecular dissection of the biochemical pathology of TCS.

KW - Animals

KW - physiology: Cell Cycle

KW - metabolism: Chromatin

KW - metabolism: DNA, Ribosomal

KW - metabolism: Dactinomycin

KW - Hela Cells

KW - Human

KW - Mice

KW - genetics: Nuclear Proteins

KW - metabolism: Nucleolus Organizer Region

KW - genetics: Phosphoproteins

KW - metabolism: Pol1 Transcription Initiation Complex Proteins

KW - Protein Binding

KW - genetics: RNA, Small Interfering

KW - genetics: Recombinant Fusion Proteins

KW - Support, Non-U.S. Gov't

KW - Support, U.S. Gov't, P.H.S.

KW - Transcription, Genetic

KW - Two-Hybrid System Techniques

U2 - 10.1073/pnas.0402492101

DO - 10.1073/pnas.0402492101

M3 - Article

VL - 101

SP - 10709

EP - 10714

JO - Proceedings of the National Academy of Sciences

JF - Proceedings of the National Academy of Sciences

SN - 0027-8424

IS - 29

ER -