Genomics

Dataset Information

154

CTCF counter-regulates cardiomyocyte development and maturation programs in the embryonic heart [4C-seq]


ABSTRACT: Analysis of chromatin architecture suggests that the 3D structure of the genome plays a major role in regulating gene expression, orchestrating the compartmentalization of chromatin and facilitating specific enhancer-promoter interactions. However, the mechanisms that control this structuring of the genome are not fully understood. We have addressed this issue by analyzing the role of CTCF, a major architectural factor in chromatin structure, in the embryonic heart. Loss of CTCF triggered an overall downregulation of the cardiac developmental program, suggesting that CTCF facilitates enhancer-promoter interactions in the developing heart. Detailed analysis of the IrxA gene cluster showed that CTCF loss leads to disruption of the heart-specific regulatory domain that surrounds Irx4, resulting in changes in expression of IrxA cluster genes and neighboring genes. In contrast to the critical role proposed for CTCF in organizing large-scale chromatin domains, our results show that CTCF preferentially mediates local regulatory interactions. Overall design: 4C-seq of E11.5 mouse embryonic hearts using Irx4 and Ndufs6 promoters and a CTCF binding site as as viewpoints. We have two conditions: control and Ctcf heart Knockout

INSTRUMENT(S): Illumina HiSeq 2000 (Mus musculus)

SUBMITTER: Miguel Manzanares  

PROVIDER: GSE99118 | GEO | 2017-08-21

SECONDARY ACCESSION(S): PRJNA387343

REPOSITORIES: GEO

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Publications


Cardiac progenitors are specified early in development and progressively differentiate and mature into fully functional cardiomyocytes. This process is controlled by an extensively studied transcriptional program. However, the regulatory events coordinating the progression of such program from development to maturation are largely unknown. Here, we show that the genome organizer CTCF is essential for cardiogenesis and that it mediates genomic interactions to coordinate cardiomyocyte differentiat  ...[more]

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