title: Distant cis-regulatory elements in human skeletal muscle differentiation.
abstract: Identifying gene regulatory elements and their target genes in human cells remains a significant challenge. Despite increasing evidence of physical interactions between distant regulatory elements and gene promoters in mammalian cells, many studies consider only promoter-proximal regulatory regions. We identify putative cis-regulatory modules (CRMs) in human skeletal muscle differentiation by combining myogenic TF binding data before and after differentiation with histone modification data in myoblasts. CRMs that are distant (>20 kb) from muscle gene promoters are common and are more likely than proximal promoter regions to show differentiation-specific changes in myogenic TF binding. We find that two of these distant CRMs, known to activate transcription in differentiating myoblasts, interact physically with gene promoters (PDLIM3 and ACTA1) during differentiation. Our results highlight the importance of considering distal CRMs in investigations of mammalian gene regulation and support the hypothesis that distant CRM-promoter looping contacts are a general mechanism of gene regulation.
authors: Division of Genetics, Department of Medicine, Brigham & Women's Hospital and Harvard Medical School, Boston, MA 02115, USA.
authors: Rachel Patton
authors: RP
authors: McCord
authors: Vicky W
authors: VW
authors: Zhou
authors: Tiffany
authors: T
authors: Yuh
authors: Martha L
authors: ML
authors: Bulyk
mesh_terms: D000465:Algorithms; D002454:Cell Differentiation / Q000235:genetics*; D002478:Cells, Cultured; D004742:Enhancer Elements, Genetic; D005786:Gene Expression Regulation; D006801:Humans; D060588:LIM Domain Proteins / Q000235:genetics / Q000378:metabolism; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism; D008840:Microfilament Proteins / Q000235:genetics / Q000378:metabolism; D018482:Muscle, Skeletal / Q000166:cytology*; D032390:Myoblasts, Smooth Muscle / Q000166:cytology* / Q000502:physiology; D011401:Promoter Regions, Genetic; D011485:Protein Binding / Q000235:genetics; D017422:Sequence Analysis, DNA; D014157:Transcription Factors / Q000235:genetics
chemical_list: D060588:LIM Domain Proteins; D035683:MicroRNAs; D008840:Microfilament Proteins; C108834:PDLIM3 protein, human; D014157:Transcription Factors