GRHL3 binding and the enhancer landscape are reorganized during transitions between different functional states of epidermal keratinocytes
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE94471 | GEO | 2017/04/12
SECONDARY ACCESSION(S): PRJNA369789
REPOSITORIES: GEO
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Project description:The genomic mechanisms underlying progressive, irreversible cell lineage commitments and differentiation, which include large scale chromatin re-organization, transcription factor binding, and chromatin modifications, have been well defined. However, we know little about the chromatin changes during transitions between transient cell states such as cell migration. Here we demonstrate the formation of unique complements of typical enhancers and super-enhancers as human progenitor keratinocytes either differentiate or migrate. Unique super-enhancers for each cellular state are linked to gene expression that confer functions associated with each cell state, and sequence variants associated with skin diseases are enriched within super-enhancers. GRHL3, a factor that promotes both differentiation and migration, exhibits prominent super-enhancer interactions in differentiating keratinocytes, while during migration, it preferentially binds to promoters along with REST, repressing the expression of migration inhibitors. Key epidermal differentiation transcription factor genes, including GRHL3, are located within super-enhancers, and many of these transcription factors in turn bind to and regulate super-enhancers. Of note, GRHL3 also represses the formation of a number of progenitor and non-keratinocyte super-enhancers in differentiating keratinocytes. Thus, coordinated GRHL3 binding and enhancer rearrangements regulate the functional states of keratinocytes.
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Project description:The genomic mechanisms underlying progressive, irreversible cell lineage commitments and differentiation, which include large scale chromatin re-organization, transcription factor binding, and chromatin modifications, have been well defined. However, we know little about the chromatin changes during transitions between transient cell states such as cell migration. Here we demonstrate the formation of unique complements of typical enhancers and super-enhancers as human progenitor keratinocytes either differentiate or migrate. Unique super-enhancers for each cellular state are linked to gene expression that confer functions associated with each cell state, and sequence variants associated with skin diseases are enriched within super-enhancers. GRHL3, a factor that promotes both differentiation and migration, exhibits prominent super-enhancer interactions in differentiating keratinocytes, while during migration, it preferentially binds to promoters along with REST, repressing the expression of migration inhibitors. Key epidermal differentiation transcription factor genes, including GRHL3, are located within super-enhancers, and many of these transcription factors in turn bind to and regulate super-enhancers. Of note, GRHL3 also represses the formation of a number of progenitor and non-keratinocyte super-enhancers in differentiating keratinocytes. Thus, coordinated GRHL3 binding and enhancer rearrangements regulate the functional states of keratinocytes.
2017-04-12 | GSE94467 | GEO
Project description:The genomic mechanisms underlying progressive, irreversible cell lineage commitments and differentiation, which include large scale chromatin re-organization, transcription factor binding, and chromatin modifications, have been well defined. However, we know little about the chromatin changes during transitions between transient cell states such as cell migration. Here we demonstrate the formation of unique complements of typical enhancers and super-enhancers as human progenitor keratinocytes either differentiate or migrate. Unique super-enhancers for each cellular state are linked to gene expression that confer functions associated with each cell state, and sequence variants associated with skin diseases are enriched within super-enhancers. GRHL3, a factor that promotes both differentiation and migration, exhibits prominent super-enhancer interactions in differentiating keratinocytes, while during migration, it preferentially binds to promoters along with REST, repressing the expression of migration inhibitors. Key epidermal differentiation transcription factor genes, including GRHL3, are located within super-enhancers, and many of these transcription factors in turn bind to and regulate super-enhancers. Of note, GRHL3 also represses the formation of a number of progenitor and non-keratinocyte super-enhancers in differentiating keratinocytes. Thus, coordinated GRHL3 binding and enhancer rearrangements regulate the functional states of keratinocytes.
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Project description:The genomic mechanisms underlying progressive, irreversible cell lineage commitments and differentiation, which include large scale chromatin re-organization, transcription factor binding, and chromatin modifications, have been well defined. However, we know little about the chromatin changes during transitions between transient cell states such as cell migration. Here we demonstrate the formation of unique complements of typical enhancers and super-enhancers as human progenitor keratinocytes either differentiate or migrate. Unique super-enhancers for each cellular state are linked to gene expression that confer functions associated with each cell state, and sequence variants associated with skin diseases are enriched within super-enhancers. GRHL3, a factor that promotes both differentiation and migration, exhibits prominent super-enhancer interactions in differentiating keratinocytes, while during migration, it preferentially binds to promoters along with REST, repressing the expression of migration inhibitors. Key epidermal differentiation transcription factor genes, including GRHL3, are located within super-enhancers, and many of these transcription factors in turn bind to and regulate super-enhancers. Of note, GRHL3 also represses the formation of a number of progenitor and non-keratinocyte super-enhancers in differentiating keratinocytes. Thus, coordinated GRHL3 binding and enhancer rearrangements regulate the functional states of keratinocytes.
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Project description:GRHL3 binding and the enhancer landscape are reorganized during transitions between different functional states of epidermal keratinocytes
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Project description:Transcription factor binding, chromatin modifications and large scale chromatin re-organization underlie progressive, irreversible cell lineage commitments and differentiation. We know little, however, about chromatin changes as cells enter transient, reversible states such as migration. Here we demonstrate that when human progenitor keratinocytes either differentiate or migrate they form complements of typical enhancers and super-enhancers that are unique for each state. Unique super-enhancers for each cellular state link to gene expression that confers functions associated with the respective cell state. These super-enhancers are also enriched for skin disease sequence variants. GRHL3, a transcription factor that promotes both differentiation and migration, binds preferentially to super-enhancers in differentiating keratinocytes, while during migration, it binds preferentially to promoters along with REST, repressing the expression of migration inhibitors. Key epidermal differentiation transcription factor genes, including GRHL3, are located within super-enhancers, and many of these transcription factors in turn bind to and regulate super-enhancers. Furthermore, GRHL3 represses the formation of a number of progenitor and non-keratinocyte super-enhancers in differentiating keratinocytes. Hence, chromatin relocates GRHL3 binding and enhancers to regulate both the irreversible commitment of progenitor keratinocytes to differentiation and their reversible transition to migration.
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