Fig. 7: Lemd3 depletion increases inter-TAD interactions at the boundaries of A and B compartments and downregulates smooth muscle contractile gene expression. | Nature Communications

Fig. 7: Lemd3 depletion increases inter-TAD interactions at the boundaries of A and B compartments and downregulates smooth muscle contractile gene expression.

From: The inner nuclear membrane protein LEMD3 organizes the 3D chromatin architecture to maintain vascular smooth muscle cell identity

Fig. 7: Lemd3 depletion increases inter-TAD interactions at the boundaries of A and B compartments and downregulates smooth muscle contractile gene expression.

a Schematic representation of topologically associating domains (TADs). RNA-seq (n = 3) was used to measure the transcriptional output. ATAC-seq (n = 3) was used to identify chromatin accessibility. b Scatter plot showing the correlation between the fold change of ATAC-seq signals and the fold change of Hi-C contact frequencies at the boundaries of the A and B compartments upon Lemd3 depletion. PCC Pearson’s correlation coefficients. c Venn diagram showing the overlap between the genes whose expression was downregulated and the genes around the closed ATAC peaks. d Transcription factor binding motif analysis of the DNA sequences of closed ATAC peaks corresponding to the genes downregulated upon Lemd3 depletion. e Bar plots showing the enriched GOBP pathways of the genes located in the TADs at the A-B boundaries with both decreased chromatin accessibility and downregulated mRNA expression. Hi-C contact maps (n = 2), histone ChIP-seq tracts (n = 2), ATAC-seq tracts (n = 3) and RNA-seq tracts (n = 3) surrounding the gene loci of Tagln (f) and Acta2 (g). The black lines delineate TAD boundaries. The bin size is 40 kb. h Scatter plot showing the statistical results of LEMD3-modulated human homologous genes. Three coordinate axes represent the distance to the nearest A-B boundary of human gene locus, the gene sequence identity compared to homologs in the rat genome, and the P value of SNPs associated with CAD from the statistical results of GWAS catalog, respectively. Dark red dots represented genes which were located at the A-B boundaries and possessed SNPs associated with CAD. Light red dots represented genes which were located at the A-B boundaries but did not possess SNPs associated with CAD. Black dots represent genes which possessed SNPs associated with CAD but were not located at the A-B boundaries. Gray dots represent genes which were not located at the A-B boundaries and did not possess SNPs associated with CAD. SNPs, single nucleotide polymorphisms. CAD, coronary artery disease. i Hi-C contact maps, ChIP-seq tracts for histone modification and regional association plot surrounding the gene locus of COL4A1 in human genome. Hi-C data were from human coronary artery smooth muscle cells, and histone modification data were from human smooth muscle cells derived from the H9 cell line. The SNPs were calculated by van der Harst P, et al. The black lines delineate TAD boundaries and the bin size is 40 kb. The black arrows indicated inter-TAD interactions at the A-B compartment boundary near the COL4A1 gene locus. CAD, coronary artery disease.

Back to article page