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Dynamics of genome reorganization during human cardiogenesis reveal an RBM20-dependent splicing factory
by
Bertero, Alessandro
, Yardimci, Galip G.
, Pabon, Lil
, Shendure, Jay
, Ramani, Vijay
, Fields, Paul A.
, Reinecke, Hans
, Noble, William S.
, Bonora, Giancarlo
, Murry, Charles E.
in
13/100
/ 13/106
/ 14/19
/ 38/23
/ 38/32
/ 45/41
/ 49/31
/ 49/39
/ 49/88
/ 631/136/532/1360
/ 631/1647/2210
/ 631/208/1792
/ 631/532/2117
/ 631/80/386
/ 82/80
/ Alternative Splicing
/ Cell Differentiation - genetics
/ Chromatin
/ Gene expression
/ Gene Expression Regulation, Developmental
/ Gene Regulatory Networks
/ Genome editing
/ Genomes
/ Heart
/ Heart - growth & development
/ Humanities and Social Sciences
/ Humans
/ Loci
/ multidisciplinary
/ Muscles
/ Myocardium - cytology
/ Myocardium - metabolism
/ Organogenesis - genetics
/ Pluripotency
/ Pluripotent Stem Cells
/ Ribonucleic acid
/ RNA
/ RNA-Binding Proteins - genetics
/ RNA-Binding Proteins - metabolism
/ RNA-Binding Proteins - physiology
/ Science
/ Science (multidisciplinary)
/ Splicing
/ Splicing factors
/ Stem cells
/ Transcription
2019
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Dynamics of genome reorganization during human cardiogenesis reveal an RBM20-dependent splicing factory
by
Bertero, Alessandro
, Yardimci, Galip G.
, Pabon, Lil
, Shendure, Jay
, Ramani, Vijay
, Fields, Paul A.
, Reinecke, Hans
, Noble, William S.
, Bonora, Giancarlo
, Murry, Charles E.
in
13/100
/ 13/106
/ 14/19
/ 38/23
/ 38/32
/ 45/41
/ 49/31
/ 49/39
/ 49/88
/ 631/136/532/1360
/ 631/1647/2210
/ 631/208/1792
/ 631/532/2117
/ 631/80/386
/ 82/80
/ Alternative Splicing
/ Cell Differentiation - genetics
/ Chromatin
/ Gene expression
/ Gene Expression Regulation, Developmental
/ Gene Regulatory Networks
/ Genome editing
/ Genomes
/ Heart
/ Heart - growth & development
/ Humanities and Social Sciences
/ Humans
/ Loci
/ multidisciplinary
/ Muscles
/ Myocardium - cytology
/ Myocardium - metabolism
/ Organogenesis - genetics
/ Pluripotency
/ Pluripotent Stem Cells
/ Ribonucleic acid
/ RNA
/ RNA-Binding Proteins - genetics
/ RNA-Binding Proteins - metabolism
/ RNA-Binding Proteins - physiology
/ Science
/ Science (multidisciplinary)
/ Splicing
/ Splicing factors
/ Stem cells
/ Transcription
2019
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Dynamics of genome reorganization during human cardiogenesis reveal an RBM20-dependent splicing factory
by
Bertero, Alessandro
, Yardimci, Galip G.
, Pabon, Lil
, Shendure, Jay
, Ramani, Vijay
, Fields, Paul A.
, Reinecke, Hans
, Noble, William S.
, Bonora, Giancarlo
, Murry, Charles E.
in
13/100
/ 13/106
/ 14/19
/ 38/23
/ 38/32
/ 45/41
/ 49/31
/ 49/39
/ 49/88
/ 631/136/532/1360
/ 631/1647/2210
/ 631/208/1792
/ 631/532/2117
/ 631/80/386
/ 82/80
/ Alternative Splicing
/ Cell Differentiation - genetics
/ Chromatin
/ Gene expression
/ Gene Expression Regulation, Developmental
/ Gene Regulatory Networks
/ Genome editing
/ Genomes
/ Heart
/ Heart - growth & development
/ Humanities and Social Sciences
/ Humans
/ Loci
/ multidisciplinary
/ Muscles
/ Myocardium - cytology
/ Myocardium - metabolism
/ Organogenesis - genetics
/ Pluripotency
/ Pluripotent Stem Cells
/ Ribonucleic acid
/ RNA
/ RNA-Binding Proteins - genetics
/ RNA-Binding Proteins - metabolism
/ RNA-Binding Proteins - physiology
/ Science
/ Science (multidisciplinary)
/ Splicing
/ Splicing factors
/ Stem cells
/ Transcription
2019
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Dynamics of genome reorganization during human cardiogenesis reveal an RBM20-dependent splicing factory
Journal Article
Dynamics of genome reorganization during human cardiogenesis reveal an RBM20-dependent splicing factory
2019
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Overview
Functional changes in spatial genome organization during human development are poorly understood. Here we report a comprehensive profile of nuclear dynamics during human cardiogenesis from pluripotent stem cells by integrating Hi-C, RNA-seq and ATAC-seq. While chromatin accessibility and gene expression show complex on/off dynamics, large-scale genome architecture changes are mostly unidirectional. Many large cardiac genes transition from a repressive to an active compartment during differentiation, coincident with upregulation. We identify a network of such gene loci that increase their association inter-chromosomally, and are targets of the muscle-specific splicing factor RBM20. Genome editing studies show that
TTN
pre-mRNA, the main RBM20-regulated transcript in the heart, nucleates RBM20 foci that drive spatial proximity between the
TTN
locus and other inter-chromosomal RBM20 targets such as
CACNA1C
and
CAMK2D
. This mechanism promotes RBM20-dependent alternative splicing of the resulting transcripts, indicating the existence of a cardiac-specific
trans
-interacting chromatin domain (TID) functioning as a splicing factory.
The spatial organization of the genome plays an important but unclearly defined role in gene regulation. Here, the authors integrate Hi-C, RNA-seq and ATAC-seq data to map cardiogenesis from pluripotent stem cells and describe an RBM20-dependent splicing factory assembling the TTN locus with other RBM20 targets.
Publisher
Nature Publishing Group UK,Nature Publishing Group,Nature Portfolio
Subject
/ 13/106
/ 14/19
/ 38/23
/ 38/32
/ 45/41
/ 49/31
/ 49/39
/ 49/88
/ 82/80
/ Cell Differentiation - genetics
/ Gene Expression Regulation, Developmental
/ Genomes
/ Heart
/ Heart - growth & development
/ Humanities and Social Sciences
/ Humans
/ Loci
/ Muscles
/ RNA
/ RNA-Binding Proteins - genetics
/ RNA-Binding Proteins - metabolism
/ RNA-Binding Proteins - physiology
/ Science
/ Splicing
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