Removable insulator facilitates higher-order chromatin remodeling and selective gene expression in the HOXA locus via the retinoic acid signaling
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE80706 | GEO | 2017/01/10
SECONDARY ACCESSION(S): PRJNA319758
REPOSITORIES: GEO
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Project description:Chromatin insulators partition the genome into the functional units to control gene expression especially in complex chromosomal regions. The CCCTC-binding factor (CTCF) is an insulator-binding protein which functions for transcriptional regulation and higher-order chromatin formation. Here we report that a removable CTCF insulator is responsible for the retinoic acid (RA)-mediated higher-order chromatin remodeling and selective gene expression in the human HOXA gene locus. Our detailed chromatin analyses characterized multiple CTCF-enriched sites and RA-responsive enhancers in this locus. These regulatory elements and transcriptionally silent HOXA genes were closely positioned under the basal condition. Notably, upon the RA signaling, the transcription factor RAR/RXR induced the loss of an adjacent CTCF binding and changed the higher-order chromatin conformation of the overall locus, establishing transcriptionally active, poised and repressive domains that were separated by stably localizing CTCF insulators. This study uncovers that removable insulator spatiotemporally switches higher-order chromatin and multiple gene activities at the chromosomal domain levels, via the cooperation of CTCF and key transcription factors.
2017-01-10 | GSE80705 | GEO
Project description:Chromatin insulators partition the genome into the functional units to control gene expression especially in complex chromosomal regions. The CCCTC-binding factor (CTCF) is an insulator-binding protein which functions for transcriptional regulation and higher-order chromatin formation. Here we report that a removable CTCF insulator is responsible for the retinoic acid (RA)-mediated higher-order chromatin remodeling and selective gene expression in the human HOXA gene locus. Our detailed chromatin analyses characterized multiple CTCF-enriched sites and RA-responsive enhancers in this locus. These regulatory elements and transcriptionally silent HOXA genes were closely positioned under the basal condition. Notably, upon the RA signaling, the transcription factor RAR/RXR induced the loss of an adjacent CTCF binding and changed the higher-order chromatin conformation of the overall locus, establishing transcriptionally active, poised and repressive domains that were separated by stably localizing CTCF insulators. This study uncovers that removable insulator spatiotemporally switches higher-order chromatin and multiple gene activities at the chromosomal domain levels, via the cooperation of CTCF and key transcription factors.
2017-01-10 | GSE65930 | GEO
Project description:Removable insulator facilitates higher-order chromatin remodeling and selective gene expression in the HOXA locus via the retinoic acid signaling
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Project description:HOX cluster genes are activated sequentially in their positional order along the chromosome during vertebrate development. This phenomenon, known as temporal colinearity, depends on transcriptional silencing of 5' HOX genes. Chromatin looping was recently identified as a conserved feature of silent HOX clusters, with CCCTC-binding factor (CTCF) binding sites located at the loop bases. However, the potential contribution of CTCF to HOX cluster silencing and the underlying mechanism have not been established. Here, we demonstrate that the HOXA locus is organized by CTCF into chromatin loops and that CTCF depletion causes significantly enhanced activation of HOXA3 to -A7, -A9 to -A11, and -A13 in response to retinoic acid, with the highest effect observed for HOXA9. Our subsequent analyses revealed that CTCF facilitates the stabilization of Polycomb repressive complex 2 (PRC2) and trimethylated lysine 27 of histone H3 (H3K27me3) at the human HOXA locus. Our results reveal that CTCF functions as a controller of HOXA cluster silencing and mediates PRC2-repressive higher-order chromatin structure.
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