Super interactive promoters provide insight into cell type-specific regulatory networks in blood lineage cell types

Existing studies of chromatin conformation have primarily focused on potential enhancers interacting with gene promoters. By contrast, the interactivity of promoters per se, while equally critical to understanding transcriptional control, has been largely unexplored, particularly in a cell type-spec...

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Veröffentlicht in:	PLoS genetics Jg. 18; H. 1; S. e1009984
Hauptverfasser:	Wen, Jia, Lagler, Taylor M., Sun, Quan, Yang, Yuchen, Chen, Jiawen, Harigaya, Yuriko, Sankaran, Vijay G., Hu, Ming, Reiner, Alexander P., Raffield, Laura M., Li, Yun
Format:	Journal Article
Sprache:	Englisch
Veröffentlicht:	United States Public Library of Science 31.01.2022 Public Library of Science (PLoS)
Schlagworte:	Biology and Life Sciences Blood Blood cells Blood Cells - metabolism CD4 antigen Cell Lineage - genetics Cell number Chromatin Conformation Disease Enhancers Ets-1 protein Gene expression Gene Regulatory Networks Genetic aspects Genetic research Genetic transcription Genome-Wide Association Study Genomes Genomics Heritability Humans Lymphocytes Lymphocytes T Medicine and Health Sciences Neutrophils Physiological aspects Promoter Regions, Genetic Promoters Proto-Oncogene Protein c-ets-1 - genetics Receptor, EphB3 - genetics Regulatory sequences Sip gene Thrombosis United States
ISSN:	1553-7404, 1553-7390, 1553-7404
Online-Zugang:	Volltext
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Zusammenfassung:	Existing studies of chromatin conformation have primarily focused on potential enhancers interacting with gene promoters. By contrast, the interactivity of promoters per se, while equally critical to understanding transcriptional control, has been largely unexplored, particularly in a cell type-specific manner for blood lineage cell types. In this study, we leverage promoter capture Hi-C data across a compendium of blood lineage cell types to identify and characterize cell type-specific super-interactive promoters (SIPs). Notably, promoter-interacting regions (PIRs) of SIPs are more likely to overlap with cell type-specific ATAC-seq peaks and GWAS variants for relevant blood cell traits than PIRs of non-SIPs. Moreover, PIRs of cell-type-specific SIPs show enriched heritability of relevant blood cell trait (s), and are more enriched with GWAS variants associated with blood cell traits compared to PIRs of non-SIPs. Further, SIP genes tend to express at a higher level in the corresponding cell type. Importantly, SIP subnetworks incorporating cell-type-specific SIPs and ATAC-seq peaks help interpret GWAS variants. Examples include GWAS variants associated with platelet count near the megakaryocyte SIP gene EPHB3 and variants associated lymphocyte count near the native CD4 T-Cell SIP gene ETS1 . Interestingly, around 25.7% ~ 39.6% blood cell traits GWAS variants residing in SIP PIR regions disrupt transcription factor binding motifs. Importantly, our analysis shows the potential of using promoter-centric analyses of chromatin spatial organization data to identify biologically important genes and their regulatory regions.
Bibliographie:	new_version ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 14 content type line 23 The authors have declared that no competing interests exist.
ISSN:	1553-7404 1553-7390 1553-7404
DOI:	10.1371/journal.pgen.1009984