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Epigenetic Basis for Heterogeneity i...

Turgeon, Paul Joseph.

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Epigenetic Basis for Heterogeneity in Vascular Cell Adhesion Molecule 1 Gene Expression in the Cytokine Activated Vascular Endothelium.

紀錄類型:	書目-電子資源 : Monograph/item
正題名/作者:	Epigenetic Basis for Heterogeneity in Vascular Cell Adhesion Molecule 1 Gene Expression in the Cytokine Activated Vascular Endothelium./
作者:	Turgeon, Paul Joseph.
出版者:	Ann Arbor : ProQuest Dissertations & Theses, : 2019,
面頁冊數:	255 p.
附註:	Source: Dissertations Abstracts International, Volume: 81-06, Section: B.
Contained By:	Dissertations Abstracts International81-06B.
標題:	Molecular biology. -
電子資源:	http://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=22623777
ISBN:	9781392610022

Epigenetic Basis for Heterogeneity in Vascular Cell Adhesion Molecule 1 Gene Expression in the Cytokine Activated Vascular Endothelium.
Turgeon, Paul Joseph.

Epigenetic Basis for Heterogeneity in Vascular Cell Adhesion Molecule 1 Gene Expression in the Cytokine Activated Vascular Endothelium. - Ann Arbor : ProQuest Dissertations & Theses, 2019 - 255 p.

Source: Dissertations Abstracts International, Volume: 81-06, Section: B.

Thesis (Ph.D.)--University of Toronto (Canada), 2019.

This item must not be sold to any third party vendors.

Homogeneous populations of mature differentiated primary cell types can display variableresponsiveness to extracellular stimuli, though little is known about the underlying mechanismsthat govern such heterogeneity at the level of gene expression. Here we show thatmorphologically homogenous human endothelial cells exhibit heterogeneous expression ofVCAM1 after TNFα stimulation. Variability in VCAM1 expression was not due to heterogeneityof intracellular signal transduction, but rather to preexisting established heterogeneous states ofpromoter DNA methylation that were generationally conserved through mitosis. Variability inDNA methylation of the VCAM1 promoter resulted in graded RelA and RNA polymerase IIbinding that gave rise to a distribution of VCAM1 transcription in the population after TNFαstimulation. Microarray analysis and single cell RNA sequencing revealed that a number ofcytokine-inducible genes shared this heterogeneous response pattern. These results show thatheritable epigenetic heterogeneity is fundamental in inflammatory signalling and highlightVCAM1 as a metastable epiallele.

ISBN: 9781392610022Subjects--Topical Terms:

517296
Molecular biology.
Subjects--Index Terms:

DNA methylation

Epigenetic Basis for Heterogeneity in Vascular Cell Adhesion Molecule 1 Gene Expression in the Cytokine Activated Vascular Endothelium.
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520 $a Homogeneous populations of mature differentiated primary cell types can display variableresponsiveness to extracellular stimuli, though little is known about the underlying mechanismsthat govern such heterogeneity at the level of gene expression. Here we show thatmorphologically homogenous human endothelial cells exhibit heterogeneous expression ofVCAM1 after TNFα stimulation. Variability in VCAM1 expression was not due to heterogeneityof intracellular signal transduction, but rather to preexisting established heterogeneous states ofpromoter DNA methylation that were generationally conserved through mitosis. Variability inDNA methylation of the VCAM1 promoter resulted in graded RelA and RNA polymerase IIbinding that gave rise to a distribution of VCAM1 transcription in the population after TNFαstimulation. Microarray analysis and single cell RNA sequencing revealed that a number ofcytokine-inducible genes shared this heterogeneous response pattern. These results show thatheritable epigenetic heterogeneity is fundamental in inflammatory signalling and highlightVCAM1 as a metastable epiallele.
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