An alternative CTCF isoform antagonizes canonical CTCF occupancy and changes chromatin architecture to promote apoptosis

CTCF plays key roles in gene regulation, chromatin insulation, imprinting, X chromosome inactivation and organizing the higher-order chromatin architecture of mammalian genomes. Previous studies have mainly focused on the roles of the canonical CTCF isoform. Here, we explore the functions of an alte...

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Published inNature communications Vol. 10; no. 1; pp. 1535 - 13
Main Authors Li, Jiao, Huang, Kaimeng, Hu, Gongcheng, Babarinde, Isaac A., Li, Yaoyi, Dong, Xiaotao, Chen, Yu-Sheng, Shang, Liping, Guo, Wenjing, Wang, Junwei, Chen, Zhaoming, Hutchins, Andrew P., Yang, Yun-Gui, Yao, Hongjie
Format Journal Article
LanguageEnglish
Published London Nature Publishing Group UK 04.04.2019
Nature Publishing Group
Nature Portfolio
Subjects
140/58
38/15
38/39
38/89
38/91
45/15
631/208/200
631/337/100/101
631/337/1645/1946
631/337/572/2102
82/83
Alternative Splicing
Apoptosis
Architecture
Binding
Binding, Competitive
CCCTC-Binding Factor - chemistry
CCCTC-Binding Factor - metabolism
CCCTC-Binding Factor - physiology
Chromatin
Chromatin - chemistry
Chromatin - metabolism
Cohesin
Deactivation
Deoxyribonucleic acid
DNA
Exons
Gene expression
Gene regulation
Genomes
Genomic imprinting
HEK293 Cells
HeLa Cells
Humanities and Social Sciences
Humans
Inactivation
Insulation
Mammals
multidisciplinary
Nucleotide sequence
Occupancy
Protein Isoforms - chemistry
Protein Isoforms - metabolism
Protein Isoforms - physiology
Science
Science (multidisciplinary)
X chromosomes
X-chromosome inactivation
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Abstract CTCF plays key roles in gene regulation, chromatin insulation, imprinting, X chromosome inactivation and organizing the higher-order chromatin architecture of mammalian genomes. Previous studies have mainly focused on the roles of the canonical CTCF isoform. Here, we explore the functions of an alternatively spliced human CTCF isoform in which exons 3 and 4 are skipped, producing a shorter isoform (CTCF-s). Functionally, we find that CTCF-s competes with the genome binding of canonical CTCF and binds a similar DNA sequence. CTCF-s binding disrupts CTCF/cohesin binding, alters CTCF-mediated chromatin looping and promotes the activation of IFI6 that leads to apoptosis. This effect is caused by an abnormal long-range interaction at the IFI6 enhancer and promoter. Taken together, this study reveals a non-canonical function for CTCF-s that antagonizes the genomic binding of canonical CTCF and cohesin, and that modulates chromatin looping and causes apoptosis by stimulating IFI6 expression. CTCF plays key roles in gene regulation, chromatin insulation and organizing the higher-order chromatin architecture of mammalian genomes. Here the authors investigate the function an alternatively spliced shorter CTCF isoform, finding that this isoform antagonizes canonical CTCF occupancy and changes chromatin architecture to promote apoptosis.
AbstractList CTCF plays key roles in gene regulation, chromatin insulation, imprinting, X chromosome inactivation and organizing the higher-order chromatin architecture of mammalian genomes. Previous studies have mainly focused on the roles of the canonical CTCF isoform. Here, we explore the functions of an alternatively spliced human CTCF isoform in which exons 3 and 4 are skipped, producing a shorter isoform (CTCF-s). Functionally, we find that CTCF-s competes with the genome binding of canonical CTCF and binds a similar DNA sequence. CTCF-s binding disrupts CTCF/cohesin binding, alters CTCF-mediated chromatin looping and promotes the activation of IFI6 that leads to apoptosis. This effect is caused by an abnormal long-range interaction at the IFI6 enhancer and promoter. Taken together, this study reveals a non-canonical function for CTCF-s that antagonizes the genomic binding of canonical CTCF and cohesin, and that modulates chromatin looping and causes apoptosis by stimulating IFI6 expression.CTCF plays key roles in gene regulation, chromatin insulation and organizing the higher-order chromatin architecture of mammalian genomes. Here the authors investigate the function an alternatively spliced shorter CTCF isoform, finding that this isoform antagonizes canonical CTCF occupancy and changes chromatin architecture to promote apoptosis.
CTCF plays key roles in gene regulation, chromatin insulation, imprinting, X chromosome inactivation and organizing the higher-order chromatin architecture of mammalian genomes. Previous studies have mainly focused on the roles of the canonical CTCF isoform. Here, we explore the functions of an alternatively spliced human CTCF isoform in which exons 3 and 4 are skipped, producing a shorter isoform (CTCF-s). Functionally, we find that CTCF-s competes with the genome binding of canonical CTCF and binds a similar DNA sequence. CTCF-s binding disrupts CTCF/cohesin binding, alters CTCF-mediated chromatin looping and promotes the activation of IFI6 that leads to apoptosis. This effect is caused by an abnormal long-range interaction at the IFI6 enhancer and promoter. Taken together, this study reveals a non-canonical function for CTCF-s that antagonizes the genomic binding of canonical CTCF and cohesin, and that modulates chromatin looping and causes apoptosis by stimulating IFI6 expression.CTCF plays key roles in gene regulation, chromatin insulation, imprinting, X chromosome inactivation and organizing the higher-order chromatin architecture of mammalian genomes. Previous studies have mainly focused on the roles of the canonical CTCF isoform. Here, we explore the functions of an alternatively spliced human CTCF isoform in which exons 3 and 4 are skipped, producing a shorter isoform (CTCF-s). Functionally, we find that CTCF-s competes with the genome binding of canonical CTCF and binds a similar DNA sequence. CTCF-s binding disrupts CTCF/cohesin binding, alters CTCF-mediated chromatin looping and promotes the activation of IFI6 that leads to apoptosis. This effect is caused by an abnormal long-range interaction at the IFI6 enhancer and promoter. Taken together, this study reveals a non-canonical function for CTCF-s that antagonizes the genomic binding of canonical CTCF and cohesin, and that modulates chromatin looping and causes apoptosis by stimulating IFI6 expression.
CTCF plays key roles in gene regulation, chromatin insulation, imprinting, X chromosome inactivation and organizing the higher-order chromatin architecture of mammalian genomes. Previous studies have mainly focused on the roles of the canonical CTCF isoform. Here, we explore the functions of an alternatively spliced human CTCF isoform in which exons 3 and 4 are skipped, producing a shorter isoform (CTCF-s). Functionally, we find that CTCF-s competes with the genome binding of canonical CTCF and binds a similar DNA sequence. CTCF-s binding disrupts CTCF/cohesin binding, alters CTCF-mediated chromatin looping and promotes the activation of IFI6 that leads to apoptosis. This effect is caused by an abnormal long-range interaction at the IFI6 enhancer and promoter. Taken together, this study reveals a non-canonical function for CTCF-s that antagonizes the genomic binding of canonical CTCF and cohesin, and that modulates chromatin looping and causes apoptosis by stimulating IFI6 expression.
CTCF plays key roles in gene regulation, chromatin insulation, imprinting, X chromosome inactivation and organizing the higher-order chromatin architecture of mammalian genomes. Previous studies have mainly focused on the roles of the canonical CTCF isoform. Here, we explore the functions of an alternatively spliced human CTCF isoform in which exons 3 and 4 are skipped, producing a shorter isoform (CTCF-s). Functionally, we find that CTCF-s competes with the genome binding of canonical CTCF and binds a similar DNA sequence. CTCF-s binding disrupts CTCF/cohesin binding, alters CTCF-mediated chromatin looping and promotes the activation of IFI6 that leads to apoptosis. This effect is caused by an abnormal long-range interaction at the IFI6 enhancer and promoter. Taken together, this study reveals a non-canonical function for CTCF-s that antagonizes the genomic binding of canonical CTCF and cohesin, and that modulates chromatin looping and causes apoptosis by stimulating IFI6 expression. CTCF plays key roles in gene regulation, chromatin insulation and organizing the higher-order chromatin architecture of mammalian genomes. Here the authors investigate the function an alternatively spliced shorter CTCF isoform, finding that this isoform antagonizes canonical CTCF occupancy and changes chromatin architecture to promote apoptosis.
CTCF plays key roles in gene regulation, chromatin insulation and organizing the higher-order chromatin architecture of mammalian genomes. Here the authors investigate the function an alternatively spliced shorter CTCF isoform, finding that this isoform antagonizes canonical CTCF occupancy and changes chromatin architecture to promote apoptosis.
ArticleNumber 1535
Author Dong, Xiaotao
Guo, Wenjing
Huang, Kaimeng
Shang, Liping
Chen, Zhaoming
Chen, Yu-Sheng
Yang, Yun-Gui
Li, Yaoyi
Wang, Junwei
Hu, Gongcheng
Babarinde, Isaac A.
Hutchins, Andrew P.
Li, Jiao
Yao, Hongjie
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BackLink https://www.ncbi.nlm.nih.gov/pubmed/30948729$$D View this record in MEDLINE/PubMed
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Snippet CTCF plays key roles in gene regulation, chromatin insulation, imprinting, X chromosome inactivation and organizing the higher-order chromatin architecture of...
CTCF plays key roles in gene regulation, chromatin insulation and organizing the higher-order chromatin architecture of mammalian genomes. Here the authors...
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SubjectTerms 140/58
38/15
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631/337/100/101
631/337/1645/1946
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82/83
Alternative Splicing
Apoptosis
Architecture
Binding
Binding, Competitive
CCCTC-Binding Factor - chemistry
CCCTC-Binding Factor - metabolism
CCCTC-Binding Factor - physiology
Chromatin
Chromatin - chemistry
Chromatin - metabolism
Cohesin
Deactivation
Deoxyribonucleic acid
DNA
Exons
Gene expression
Gene regulation
Genomes
Genomic imprinting
HEK293 Cells
HeLa Cells
Humanities and Social Sciences
Humans
Inactivation
Insulation
Mammals
multidisciplinary
Nucleotide sequence
Occupancy
Protein Isoforms - chemistry
Protein Isoforms - metabolism
Protein Isoforms - physiology
Science
Science (multidisciplinary)
X chromosomes
X-chromosome inactivation
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Title An alternative CTCF isoform antagonizes canonical CTCF occupancy and changes chromatin architecture to promote apoptosis
URI https://link.springer.com/article/10.1038/s41467-019-08949-w
https://www.ncbi.nlm.nih.gov/pubmed/30948729
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https://pubmed.ncbi.nlm.nih.gov/PMC6449404
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Volume 10
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