title: DNase-seq predicts regions of rotational nucleosome stability across diverse human cell types.
abstract: DNase-seq is primarily used to identify nucleosome-depleted DNase I hypersensitive (DHS) sites genome-wide that correspond to active regulatory elements. However, ≈ 40 yr ago it was demonstrated that DNase I also digests with a ≈ 10-bp periodicity around nucleosomes matching the exposure of the DNA minor groove as it wraps around histones. Here, we use DNase-seq data from 49 samples representing diverse cell types to reveal this digestion pattern at individual loci and predict genomic locations where nucleosome rotational positioning, the orientation of DNA with respect to the histone surface, is stably maintained. We call these regions DNase I annotated regions of nucleosome stability (DARNS). Compared to MNase-seq experiments, we show DARNS correspond well to annotated nucleosomes. Interestingly, many DARNS are positioned over only one side of annotated nucleosomes, suggesting that the periodic digestion pattern attenuates over the nucleosome dyad. DARNS reproduce the arrangement of nucleosomes around transcription start sites and are depleted at ubiquitous DHS sites. We also generated DARNS from multiple lymphoblast cell line (LCL) samples. We found that LCL DARNS were enriched at DHS sites present in most of the original 49 samples but absent in LCLs, while multi-cell-type DARNS were enriched at LCL-specific DHS sites. This indicates that variably open DHS sites are often occupied by rotationally stable nucleosomes in cell types where the DHS site is closed. DARNS provide additional information about precise DNA orientation within individual nucleosomes not available from other nucleosome positioning assays and contribute to understanding the role of chromatin in gene regulation.
authors: Institute for Genome Sciences and Policy, Duke University, Durham, North Carolina 27708, USA.
authors: Deborah R
authors: DR
authors: Winter
authors: Lingyun
authors: L
authors: Song
authors: Sayan
authors: S
authors: Mukherjee
authors: Terrence S
authors: TS
authors: Furey
authors: Gregory E
authors: GE
authors: Crawford
mesh_terms: D001665:Binding Sites; D002460:Cell Line; D004247:DNA / Q000235:genetics* / Q000378:metabolism*; D003850:Deoxyribonuclease I / Q000378:metabolism; D003851:Deoxyribonucleases / Q000378:metabolism*; D056426:Genetic Loci; D023281:Genomics; D006801:Humans; D009707:Nucleosomes / Q000235:genetics* / Q000378:metabolism*; D011485:Protein Binding
chemical_list: D009707:Nucleosomes; D004247:DNA; D003851:Deoxyribonucleases; D003850:Deoxyribonuclease I
references: Cell. 1979 Apr;16(4):797-806
references: 455449
references: Annu Rev Biochem. 1988;57:159-97
references: 3052270
references: Cell. 1978 Jul;14(3):611-27
references: 688384
references: Genome Res. 2011 Oct;21(10):1757-67
references: 21750106
references: Genome Res. 2002 Jun;12(6):996-1006
references: 12045153
references: Cell. 2008 Mar 7;132(5):887-98
references: 18329373
references: Proc Natl Acad Sci U S A. 1979 Jan;76(1):200-3
references: 284332
references: Nat Rev Genet. 2009 Mar;10(3):161-72
references: 19204718
references: Nature. 2006 Aug 17;442(7104):772-8
references: 16862119
references: Cell. 2008 Jan 25;132(2):311-22
references: 18243105
references: Cell. 2007 Feb 23;128(4):651-4
references: 17320503
references: Science. 2010 Apr 9;328(5975):235-9
references: 20299549
references: Genome Res. 2012 Dec;22(12):2399-408
references: 23100115
references: Proc Natl Acad Sci U S A. 1980 Jul;77(7):3816-20
references: 6933438
references: J Biol Chem. 1995 Apr 14;270(15):8373-6
references: 7721727
references: PLoS Comput Biol. 2008 Sep 12;4(9):e1000175
references: 18787693
references: Nature. 2007 Mar 29;446(7135):572-6
references: 17392789
references: J Mol Biol. 2004 Jan 30;335(5):1199-211
references: 14729337
references: Nat Struct Mol Biol. 2010 Aug;17(8):923
references: 20683475
references: J Mol Biol. 1986 Oct 20;191(4):659-75
references: 3806678
references: Genome Res. 2011 Nov;21(11):1863-71
references: 21750105
references: Nature. 2012 Sep 6;489(7414):75-82
references: 22955617
references: Nature. 2012 Sep 6;489(7414):57-74
references: 22955616
references: Nucleic Acids Res. 1974 Nov;1(11):1573-8
references: 10793712
references: Genome Res. 2011 Oct;21(10):1650-8
references: 21795385
references: Nucleic Acids Res. 2000 Aug 15;28(16):3092-9
references: 10931924
references: Nature. 2012 Feb 05;482(7385):390-4
references: 22307276
references: Nat Struct Mol Biol. 2009 Aug;16(8):847-52
references: 19620965
references: Genome Res. 2007 Jun;17(6):877-85
references: 17179217
references: Nature. 2003 May 8;423(6936):145-50
references: 12736678
references: Genome Res. 2009 Aug;19(8):1480-96
references: 19451592
references: Nature. 2003 Jan 23;421(6921):448-53
references: 12540921
references: Nature. 2010 Jul 15;466(7304):388-92
references: 20512117
references: Nature. 2011 May 22;474(7352):516-20
references: 21602827
references: Nature. 2009 Mar 19;458(7236):362-6
references: 19092803
references: PLoS Genet. 2012;8(11):e1003036
references: 23166509
references: Nature. 2012 Jun 28;486(7404):496-501
references: 22722846
references: Genome Res. 2008 Jul;18(7):1073-83
references: 18550805