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Spatially-restricted and ontogenically-distinct hepatic macrophages are required for tissue repair.

ABSTRACT: Spatially-restricted and ontogenically-distinct hepatic macrophages are required for tissue repair.

PROVIDER: PRJNA1179315 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR31146548.fastq.gz	Fastqsanger.gz
	SRR31146549.fastq.gz	Fastqsanger.gz
	SRR31146550.fastq.gz	Fastqsanger.gz
	SRR31146551.fastq.gz	Fastqsanger.gz
	SRR31146552.fastq.gz	Fastqsanger.gz

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Spatially-restricted and ontogenically-distinct hepatic macrophages are required for tissue repair.

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Project description:Interactions between the nuclear lamina (NL) and chromatin are thought to occur through large lamin association domains (LADs) and correlate with gene repression in these domains. We show that binding of lamin A/C (LMNA) to promoters occurs on discrete domains that are associated with distinct transcriptional outputs. Chromatin immunoprecipitation identifies thousands of LMNA-bound promoters, primarily linked to signaling functions. LMNA often occupies narrow domains on promoters, yet LMNA-bound promoters are often contiguous. LMNA-bound genes are overall repressed, but repression correlates with co-enrichment in repressive histone marks rather than LMNA occupancy per se. Genes marked by LMNA and H3K4me3 escape LMNA-associated repression in the absence of repressive histone marks. Positioning of LMNA on promoters relative to the TSS correlates with distinct transcriptional outputs: whereas upstream-distal binding can be transcriptionally permissive, TSS occupancy is associated with promoter inactivity. Perturbation in NL organization causes reorganization of lamin promoter occupancy and uncouples LMNA binding from promoter inactivity. Our results show the existence of many spatially restricted LMNA binding events on promoter regions, with distinct position-dependent transcriptional outputs. Total RNA obtained from ASCs and ASCs depleted of LMNA (LMNA-KD) and processed for microarray hybridization.

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