Epigenetic and Transcriptional Networks Underlying Atrial Fibrillation

Antoinette F van Ouwerkerk; Amelia W Hall; Zachary A Kadow; Sonja Lazarevic; Jasmeet S Reyat; Nathan R Tucker; Rangarajan D Nadadur; Fernanda M Bosada; Valerio Bianchi; Patrick T Ellinor; Larissa Fabritz; James F Martin; Wouter de Laat; Paulus Kirchhof; Ivan P Moskowitz; Vincent M Christoffels

doi:10.1161/CIRCRESAHA.120.316574

Epigenetic and Transcriptional Networks Underlying Atrial Fibrillation

Antoinette F van Ouwerkerk, Amelia W Hall, Zachary A Kadow, Sonja Lazarevic, Jasmeet S Reyat, Nathan R Tucker, Rangarajan D Nadadur, Fernanda M Bosada, Valerio Bianchi, Patrick T Ellinor, Larissa Fabritz, James F Martin, Wouter de Laat, Paulus Kirchhof, Ivan P Moskowitz, Vincent M Christoffels

Hubrecht Institute

Onderzoeksoutput: Bijdrage aan wetenschappelijk tijdschrift/periodieke uitgave › Boek/film/artikelrecensie › Wetenschappelijk

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Genome-wide association studies have uncovered over a 100 genetic loci associated with atrial fibrillation (AF), the most common arrhythmia. Many of the top AF-associated loci harbor key cardiac transcription factors, including PITX2, TBX5, PRRX1, and ZFHX3. Moreover, the vast majority of the AF-associated variants lie within noncoding regions of the genome where causal variants affect gene expression by altering the activity of transcription factors and the epigenetic state of chromatin. In this review, we discuss a transcriptional regulatory network model for AF defined by effector genes in Genome-wide association studies loci. We describe the current state of the field regarding the identification and function of AF-relevant gene regulatory networks, including variant regulatory elements, dose-sensitive transcription factor functionality, target genes, and epigenetic states. We illustrate how altered transcriptional networks may impact cardiomyocyte function and ionic currents that impact AF risk. Last, we identify the need for improved tools to identify and functionally test transcriptional components to define the links between genetic variation, epigenetic gene regulation, and atrial function.

Originele taal-2	Engels
Pagina's (van-tot)	34-50
Aantal pagina's	17
Tijdschrift	Circulation Research
Volume	127
Nummer van het tijdschrift	1
DOI's	https://doi.org/10.1161/CIRCRESAHA.120.316574
Status	Gepubliceerd - 19 jun. 2020

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10.1161/CIRCRESAHA.120.316574

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van Ouwerkerk, A. F., Hall, A. W., Kadow, Z. A., Lazarevic, S., Reyat, J. S., Tucker, N. R., Nadadur, R. D., Bosada, F. M., Bianchi, V., Ellinor, P. T., Fabritz, L., Martin, J. F., de Laat, W., Kirchhof, P., Moskowitz, I. P., & Christoffels, V. M. (2020). Epigenetic and Transcriptional Networks Underlying Atrial Fibrillation. Circulation Research, 127(1), 34-50. https://doi.org/10.1161/CIRCRESAHA.120.316574

van Ouwerkerk, Antoinette F ; Hall, Amelia W ; Kadow, Zachary A ; Lazarevic, Sonja ; Reyat, Jasmeet S ; Tucker, Nathan R ; Nadadur, Rangarajan D ; Bosada, Fernanda M ; Bianchi, Valerio ; Ellinor, Patrick T ; Fabritz, Larissa ; Martin, James F ; de Laat, Wouter ; Kirchhof, Paulus ; Moskowitz, Ivan P ; Christoffels, Vincent M. / Epigenetic and Transcriptional Networks Underlying Atrial Fibrillation. In: Circulation Research. 2020 ; Vol. 127, Nr. 1. blz. 34-50.

@article{2c8f3efef06844799f7d33fdbe6eef1e,

title = "Epigenetic and Transcriptional Networks Underlying Atrial Fibrillation",

abstract = "Genome-wide association studies have uncovered over a 100 genetic loci associated with atrial fibrillation (AF), the most common arrhythmia. Many of the top AF-associated loci harbor key cardiac transcription factors, including PITX2, TBX5, PRRX1, and ZFHX3. Moreover, the vast majority of the AF-associated variants lie within noncoding regions of the genome where causal variants affect gene expression by altering the activity of transcription factors and the epigenetic state of chromatin. In this review, we discuss a transcriptional regulatory network model for AF defined by effector genes in Genome-wide association studies loci. We describe the current state of the field regarding the identification and function of AF-relevant gene regulatory networks, including variant regulatory elements, dose-sensitive transcription factor functionality, target genes, and epigenetic states. We illustrate how altered transcriptional networks may impact cardiomyocyte function and ionic currents that impact AF risk. Last, we identify the need for improved tools to identify and functionally test transcriptional components to define the links between genetic variation, epigenetic gene regulation, and atrial function.",

author = "{van Ouwerkerk}, {Antoinette F} and Hall, {Amelia W} and Kadow, {Zachary A} and Sonja Lazarevic and Reyat, {Jasmeet S} and Tucker, {Nathan R} and Nadadur, {Rangarajan D} and Bosada, {Fernanda M} and Valerio Bianchi and Ellinor, {Patrick T} and Larissa Fabritz and Martin, {James F} and {de Laat}, Wouter and Paulus Kirchhof and Moskowitz, {Ivan P} and Christoffels, {Vincent M}",

year = "2020",

month = jun,

day = "19",

doi = "10.1161/CIRCRESAHA.120.316574",

language = "English",

volume = "127",

pages = "34--50",

journal = "Circulation Research",

issn = "0009-7330",

publisher = "Lippincott Williams & Wilkins",

number = "1",

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van Ouwerkerk, AF, Hall, AW, Kadow, ZA, Lazarevic, S, Reyat, JS, Tucker, NR, Nadadur, RD, Bosada, FM, Bianchi, V, Ellinor, PT, Fabritz, L, Martin, JF, de Laat, W, Kirchhof, P, Moskowitz, IP & Christoffels, VM 2020, 'Epigenetic and Transcriptional Networks Underlying Atrial Fibrillation', Circulation Research, vol. 127, nr. 1, blz. 34-50. https://doi.org/10.1161/CIRCRESAHA.120.316574

Epigenetic and Transcriptional Networks Underlying Atrial Fibrillation. / van Ouwerkerk, Antoinette F; Hall, Amelia W; Kadow, Zachary A; Lazarevic, Sonja; Reyat, Jasmeet S; Tucker, Nathan R; Nadadur, Rangarajan D; Bosada, Fernanda M; Bianchi, Valerio; Ellinor, Patrick T; Fabritz, Larissa; Martin, James F; de Laat, Wouter; Kirchhof, Paulus; Moskowitz, Ivan P; Christoffels, Vincent M.

In: Circulation Research, Vol. 127, Nr. 1, 19.06.2020, blz. 34-50.

Onderzoeksoutput: Bijdrage aan wetenschappelijk tijdschrift/periodieke uitgave › Boek/film/artikelrecensie › Wetenschappelijk

TY - JOUR

T1 - Epigenetic and Transcriptional Networks Underlying Atrial Fibrillation

AU - van Ouwerkerk, Antoinette F

AU - Hall, Amelia W

AU - Kadow, Zachary A

AU - Lazarevic, Sonja

AU - Reyat, Jasmeet S

AU - Tucker, Nathan R

AU - Nadadur, Rangarajan D

AU - Bosada, Fernanda M

AU - Bianchi, Valerio

AU - Ellinor, Patrick T

AU - Fabritz, Larissa

AU - Martin, James F

AU - de Laat, Wouter

AU - Kirchhof, Paulus

AU - Moskowitz, Ivan P

AU - Christoffels, Vincent M

PY - 2020/6/19

Y1 - 2020/6/19

N2 - Genome-wide association studies have uncovered over a 100 genetic loci associated with atrial fibrillation (AF), the most common arrhythmia. Many of the top AF-associated loci harbor key cardiac transcription factors, including PITX2, TBX5, PRRX1, and ZFHX3. Moreover, the vast majority of the AF-associated variants lie within noncoding regions of the genome where causal variants affect gene expression by altering the activity of transcription factors and the epigenetic state of chromatin. In this review, we discuss a transcriptional regulatory network model for AF defined by effector genes in Genome-wide association studies loci. We describe the current state of the field regarding the identification and function of AF-relevant gene regulatory networks, including variant regulatory elements, dose-sensitive transcription factor functionality, target genes, and epigenetic states. We illustrate how altered transcriptional networks may impact cardiomyocyte function and ionic currents that impact AF risk. Last, we identify the need for improved tools to identify and functionally test transcriptional components to define the links between genetic variation, epigenetic gene regulation, and atrial function.

AB - Genome-wide association studies have uncovered over a 100 genetic loci associated with atrial fibrillation (AF), the most common arrhythmia. Many of the top AF-associated loci harbor key cardiac transcription factors, including PITX2, TBX5, PRRX1, and ZFHX3. Moreover, the vast majority of the AF-associated variants lie within noncoding regions of the genome where causal variants affect gene expression by altering the activity of transcription factors and the epigenetic state of chromatin. In this review, we discuss a transcriptional regulatory network model for AF defined by effector genes in Genome-wide association studies loci. We describe the current state of the field regarding the identification and function of AF-relevant gene regulatory networks, including variant regulatory elements, dose-sensitive transcription factor functionality, target genes, and epigenetic states. We illustrate how altered transcriptional networks may impact cardiomyocyte function and ionic currents that impact AF risk. Last, we identify the need for improved tools to identify and functionally test transcriptional components to define the links between genetic variation, epigenetic gene regulation, and atrial function.

U2 - 10.1161/CIRCRESAHA.120.316574

DO - 10.1161/CIRCRESAHA.120.316574

M3 - Book/Film/Article review

C2 - 32717170

VL - 127

SP - 34

EP - 50

JO - Circulation Research

JF - Circulation Research

SN - 0009-7330

IS - 1

ER -

Epigenetic and Transcriptional Networks Underlying Atrial Fibrillation

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