PMC:3492650 / 10949-13940
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{"target":"https://pubannotation.org/docs/sourcedb/PMC/sourceid/3492650","sourcedb":"PMC","sourceid":"3492650","source_url":"https://www.ncbi.nlm.nih.gov/pmc/3492650","text":"Chromatin structure defined by FAIRE and histone modifications\nThe chromatin structure was analyzed by comparing genomic regions defined by FAIRE with histone modification sites detected by ChIP-Seq in a breast cancer cell line, MCF-7. Due to the limited information of FAIRE-chip data, we analyzed regions enriched in human chromosomes 8, 11, and 12. The overall positions of regulatory elements and histone modifications relative to TSS are depicted in Fig. 1A. The k-clustered pattern, depending on their enrichment level, showed that most H3K4me3 and H3K9/14ac modifications, known as active chromatin marks, were enriched near TSS, whereas H3K27me3, a repressive mark, was not. Many regulatory elements detected by FAIRE-chip were also located near TSS, reflecting that promoters are one of the major nucleosome-free sites. The relative positions of 3 histone modification enrichments (H3K4me1, H3K4me3, and H3K9/14ac) were aligned to the center of FAIRE signals and overlapped within ± 1-kb regions from TSSs (Fig. 1B). The H3K4me1 had a broader spectrum than the other 2 modifications in ± 0.5-1.5-kb regions. These results implied that regulatory elements were highly correlated with active histone modifications and associated with open chromatin structure.\nA total of 2,804 regulatory elements from FAIRE-chip data were identified by CisGenome analysis, and the number of ChIP-Seq peaks was calculated using HOMER program: 18,938 for HK4me1, 4,516 for H3K4me3, 5,763 for H3K9/14ac, and 3,324 for H3K27me3 (Table 1). The FAIRE sites were located in especially functional element-related regions: promoters (32.2% of FAIRE sites analyzed), 4 kb upstream of promoters (3.2%), gene bodies (39.1%), and intergenic regions (25.4%). In particular, the highest enrichment of FAIREs in promoters could be identified by the normalization in quantitative comparison of FAIRE profiles (i.e., the total number of peaks/total length of each of genomic feature). We selected the overlapping regulatory elements of FAIRE signals with ChIP-Seq peaks and looked at their co-occurrence; the regulatory elements with H3K4me1 (FAIRE-H3K4me1) were 1,006; FAIRE-H3K4me3, 1,000; and FAIRE-H3K9/14ac, 1,264. Among them, 334 elements showed enrichment of both H3K4me3 and H3K9/14ac (Fig. 1C). This relationship was further confirmed by the distribution of FAIRE-histone modifications, shown in Fig. 1D. The highest population of FAIRE-H3K4me3 and FAIRE-H3K9/14ac was observed immediately downstream of TSS (Fig. 1D). A weak enrichment of FAIRE-H3K4me1 elements was detected upstream of TSS, where a shoulder peak of FAIRE-H3K4me1 and H3K4me3 was positioned. For example, 4 FAIRE regulatory elements of cyclin D1 (CCND1), involved in tumorigenesis as a cell cycle regulator, were located at the promoter and overlapped with peaks of H3K4me3 and H3K9/14ac but not with H3K4me1 or H3K27me3 (Fig. 1E). Instead, the H3K4me1 peaks in the CCND1 gene locus were expanded along the gene body and far upstream of TSS.","divisions":[{"label":"Title","span":{"begin":0,"end":62}}],"tracks":[]}