GSE26320, Chromatin state dynamics in nine human cell types


Chromatin profiling has emerged as a powerful means for annotating genomic elements and detecting regulatory activity. Here we generate and analyze a compendium of epigenomic maps for nine chromatin marks across nine cell types, in order to systematically characterize cis-regulatory elements, their cell type-specificities, and their functional interactions. We first identify recurrent combinations of histone modifications and use them to annotate diverse regulatory elements including promoters, enhancers, transcripts and insulators in each cell type. We next characterize the dynamics of these elements, revealing meaningful patterns of activity for promoter states and exquisite cell type-selectivity for enhancer states. We define multi-cell activity profiles that reflect the patterns of enhancer state activity across cell types, as well as analogous profiles for gene expression, regulatory motif enrichments, and expression of the corresponding regulators. We use correlations between these profiles to link enhancers to putative target genes, to infer cell type-specific activators and repressors, and to predict and validate functional regulator binding motifs in specific chromatin states. These functional annotations and regulatory predictions enable us to revisit intergenic single-nucleotide polymorphisms (SNPs) associated with human disease in genome-wide association studies (GWAS). We find that for several diseases, top-scoring SNPs are precisely positioned within enhancer elements specifically active in relevant cell types. In several cases a disease variant affects a motif instance for one of the predicted causal regulators, thus providing a potential mechanistic explanation for the disease association. Our study presents a general framework for applying multi-cell chromatin state analysis to decipher cis-regulatory connections and their role in health and disease.

Overall design

CTCF, H3K27ac, H3K27me3, H3K4me1, H3K4me2, H3K4me3, H3K9ac, H4K20me1, H3K36me3 and Whole Cell Extract (WCE) were profiled with ChIP-seq in 9 cell types (H1, GM12878, K562, HepG2, Huvec, HSMM, NHLF, NHEK, HMEC) in almost all cases in duplicate. Also H3K9me3 was profiled with ChIP-seq in K562.


Files downloaded from GEO series: GSE26320
Input file format: BED


From Human Mar. 2006 (NCBI36/hg18) Assembly

Filename Description Feature GEO-ID
1 GSM646314_GM12878_CTCF_rep1.sga GM12878 CTCF rep1 CTCF GSM646314
2 GSM646315_GM12878_CTCF_rep2.sga GM12878 CTCF rep2 CTCF GSM646315
3 GSM646316_GM12878_H3K27ac_rep1.sga GM12878 H3K27ac rep1 H3K27ac GSM646316
4 GSM646317_GM12878_H3K27ac_rep2.sga GM12878 H3K27ac rep2 H3K27ac GSM646317
5 GSM646318_GM12878_H3K27me3_rep1.sga GM12878 H3K27me3 rep1 H3K27me3 GSM646318
6 GSM646319_GM12878_H3K27me3_rep2.sga GM12878 H3K27me3 rep2 H3K27me3 GSM646319
7 GSM646320_GM12878_H3K36me3_rep1.sga GM12878 H3K36me3 rep1 H3K36me3 GSM646320
8 GSM646321_GM12878_H3K36me3_rep2.sga GM12878 H3K36me3 rep2 H3K36me3 GSM646321
9 GSM646322_GM12878_H3K4me1_rep1.sga GM12878 H3K4me1 rep1 H3K4me1 GSM646322
10 GSM646323_GM12878_H3K4me1_rep2.sga GM12878 H3K4me1 rep2 H3K4me1 GSM646323
11 GSM646324_GM12878_H3K4me2_rep1.sga GM12878 H3K4me2 rep1 H3K4me2 GSM646324
12 GSM646325_GM12878_H3K4me2_rep2.sga GM12878 H3K4me2 rep2 H3K4me2 GSM646325
13 GSM646326_GM12878_H3K4me3_rep1.sga GM12878 H3K4me3 rep1 H3K4me3 GSM646326
14 GSM646327_GM12878_H3K4me3_rep2.sga GM12878 H3K4me3 rep2 H3K4me3 GSM646327
15 GSM646328_GM12878_H3K9ac_rep1.sga GM12878 H3K9ac rep1 H3K9ac GSM646328
16 GSM646329_GM12878_H3K9ac_rep2.sga GM12878 H3K9ac rep2 H3K9ac GSM646329
17 GSM646330_GM12878_H4K20me1_rep1.sga GM12878 H4K20me1 rep1 H4K20me1 GSM646330
18 GSM646331_GM12878_H4K20me1_rep2.sga GM12878 H4K20me1 rep2 H4K20me1 GSM646331
19 GSM646332_GM12878_WCE_rep1.sga GM12878 WCE rep1 WCE GSM646332
20 GSM646333_GM12878_WCE_rep2.sga GM12878 WCE rep2 WCE GSM646333
21 GSM646334_H1_CTCF_rep1.sga H1 CTCF rep1 CTCF GSM646334
22 GSM646335_H1_CTCF_rep2.sga H1 CTCF rep2 CTCF GSM646335
23 GSM646336_H1_H3K27ac_rep1.sga H1 H3K27ac rep1 H3K27ac GSM646336
24 GSM646337_H1_H3K27me3_rep1.sga H1 H3K27me3 rep1 H3K27me3 GSM646337
25 GSM646338_H1_H3K27me3_rep2.sga H1 H3K27me3 rep2 H3K27me3 GSM646338
26 GSM646339_H1_H3K36me3_rep1.sga H1 H3K36me3 rep1 H3K36me3 GSM646339
27 GSM646340_H1_H3K36me3_rep2.sga H1 H3K36me3 rep2 H3K36me3 GSM646340
28 GSM646341_H1_H3K4me1_rep1.sga H1 H3K4me1 rep1 H3K4me1 GSM646341
29 GSM646342_H1_H3K4me1_rep2.sga H1 H3K4me1 rep2 H3K4me1 GSM646342
30 GSM646343_H1_H3K4me2_rep1.sga H1 H3K4me2 rep1 H3K4me2 GSM646343
31 GSM646344_H1_H3K4me2_rep2.sga H1 H3K4me2 rep2 H3K4me2 GSM646344
32 GSM646345_H1_H3K4me3_rep1.sga H1 H3K4me3 rep1 H3K4me3 GSM646345
33 GSM646346_H1_H3K4me3_rep2.sga H1 H3K4me3 rep2 H3K4me3 GSM646346
34 GSM646347_H1_H3K9ac_rep1.sga H1 H3K9ac rep1 H3K9ac GSM646347
35 GSM646348_H1_H3K9ac_rep2.sga H1 H3K9ac rep2 H3K9ac GSM646348
36 GSM646349_H1_H4K20me1_rep1.sga H1 H4K20me1 rep1 H4K20me1 GSM646349
37 GSM646350_H1_H4K20me1_rep2.sga H1 H4K20me1 rep2 H4K20me1 GSM646350
38 GSM646351_H1_WCE_rep1.sga H1 WCE rep1 WCE GSM646351
39 GSM646352_H1_WCE_rep2.sga H1 WCE rep2 WCE GSM646352
40 GSM646353_HepG2_CTCF_rep1.sga HepG2 CTCF rep1 CTCF GSM646353
41 GSM646354_HepG2_CTCF_rep2.sga HepG2 CTCF rep2 CTCF GSM646354
42 GSM646355_HepG2_H3K27ac_rep1.sga HepG2 H3K27ac rep1 H3K27ac GSM646355
43 GSM646356_HepG2_H3K27ac_rep2.sga HepG2 H3K27ac rep2 H3K27ac GSM646356
44 GSM646357_HepG2_H3K27me3_rep1.sga HepG2 H3K27me3 rep1 H3K27me3 GSM646357
45 GSM646358_HepG2_H3K27me3_rep2.sga HepG2 H3K27me3 rep2 H3K27me3 GSM646358
46 GSM646359_HepG2_H3K36me3_rep1.sga HepG2 H3K36me3 rep1 H3K36me3 GSM646359
47 GSM646360_HepG2_H3K36me3_rep2.sga HepG2 H3K36me3 rep2 H3K36me3 GSM646360
48 GSM646361_HepG2_H3K4me1_rep1.sga HepG2 H3K4me1 rep1 H3K4me1 GSM646361
49 GSM646362_HepG2_H3K4me2_rep1.sga HepG2 H3K4me2 rep1 H3K4me2 GSM646362
50 GSM646363_HepG2_H3K4me2_rep2.sga HepG2 H3K4me2 rep2 H3K4me2 GSM646363
51 GSM646364_HepG2_H3K4me3_rep1.sga HepG2 H3K4me3 rep1 H3K4me3 GSM646364
52 GSM646365_HepG2_H3K4me3_rep2.sga HepG2 H3K4me3 rep2 H3K4me3 GSM646365
53 GSM646366_HepG2_H3K9ac_rep1.sga HepG2 H3K9ac rep1 H3K9ac GSM646366
54 GSM646367_HepG2_H3K9ac_rep2.sga HepG2 H3K9ac rep2 H3K9ac GSM646367
55 GSM646368_HepG2_H4K20me1_rep1.sga HepG2 H4K20me1 rep1 H4K20me1 GSM646368
56 GSM646369_HepG2_H4K20me1_rep2.sga HepG2 H4K20me1 rep2 H4K20me1 GSM646369
57 GSM646370_HepG2_WCE_rep1.sga HepG2 WCE rep1 WCE GSM646370
58 GSM646371_HepG2_WCE_rep2.sga HepG2 WCE rep2 WCE GSM646371
59 GSM646372_HMEC_CTCF_rep1.sga HMEC CTCF rep1 CTCF GSM646372
60 GSM646373_HMEC_CTCF_rep2.sga HMEC CTCF rep2 CTCF GSM646373
61 GSM646374_HMEC_H3K27ac_rep1.sga HMEC H3K27ac rep1 H3K27ac GSM646374
62 GSM646375_HMEC_H3K27ac_rep2.sga HMEC H3K27ac rep2 H3K27ac GSM646375
63 GSM646376_HMEC_H3K27me3_rep1.sga HMEC H3K27me3 rep1 H3K27me3 GSM646376
64 GSM646377_HMEC_H3K27me3_rep2.sga HMEC H3K27me3 rep2 H3K27me3 GSM646377
65 GSM646378_HMEC_H3K36me3_rep1.sga HMEC H3K36me3 rep1 H3K36me3 GSM646378
66 GSM646379_HMEC_H3K36me3_rep2.sga HMEC H3K36me3 rep2 H3K36me3 GSM646379
67 GSM646380_HMEC_H3K4me1_rep1.sga HMEC H3K4me1 rep1 H3K4me1 GSM646380
68 GSM646381_HMEC_H3K4me1_rep2.sga HMEC H3K4me1 rep2 H3K4me1 GSM646381
69 GSM646382_HMEC_H3K4me2_rep1.sga HMEC H3K4me2 rep1 H3K4me2 GSM646382
70 GSM646383_HMEC_H3K4me2_rep2.sga HMEC H3K4me2 rep2 H3K4me2 GSM646383
71 GSM646384_HMEC_H3K4me3_rep1.sga HMEC H3K4me3 rep1 H3K4me3 GSM646384
72 GSM646385_HMEC_H3K4me3_rep2.sga HMEC H3K4me3 rep2 H3K4me3 GSM646385
73 GSM646386_HMEC_H3K9ac_rep1.sga HMEC H3K9ac rep1 H3K9ac GSM646386
74 GSM646387_HMEC_H3K9ac_rep2.sga HMEC H3K9ac rep2 H3K9ac GSM646387
75 GSM646388_HMEC_H4K20me1_rep1.sga HMEC H4K20me1 rep1 H4K20me1 GSM646388
76 GSM646389_HMEC_H4K20me1_rep2.sga HMEC H4K20me1 rep2 H4K20me1 GSM646389
77 GSM646390_HMEC_WCE_rep1.sga HMEC WCE rep1 WCE GSM646390
78 GSM646391_HMEC_WCE_rep2.sga HMEC WCE rep2 WCE GSM646391
79 GSM646392_HSMM_CTCF_rep1.sga HSMM CTCF rep1 CTCF GSM646392
80 GSM646393_HSMM_CTCF_rep2.sga HSMM CTCF rep2 CTCF GSM646393
81 GSM646394_HSMM_H3K27ac_rep1.sga HSMM H3K27ac rep1 H3K27ac GSM646394
82 GSM646395_HSMM_H3K27ac_rep2.sga HSMM H3K27ac rep2 H3K27ac GSM646395
83 GSM646396_HSMM_H3K27me3_rep1.sga HSMM H3K27me3 rep1 H3K27me3 GSM646396
84 GSM646397_HSMM_H3K27me3_rep2.sga HSMM H3K27me3 rep2 H3K27me3 GSM646397
85 GSM646398_HSMM_H3K36me3_rep1.sga HSMM H3K36me3 rep1 H3K36me3 GSM646398
86 GSM646399_HSMM_H3K36me3_rep2.sga HSMM H3K36me3 rep2 H3K36me3 GSM646399
87 GSM646400_HSMM_H3K4me1_rep1.sga HSMM H3K4me1 rep1 H3K4me1 GSM646400
88 GSM646401_HSMM_H3K4me1_rep2.sga HSMM H3K4me1 rep2 H3K4me1 GSM646401
89 GSM646402_HSMM_H3K4me2_rep1.sga HSMM H3K4me2 rep1 H3K4me2 GSM646402
90 GSM646403_HSMM_H3K4me2_rep2.sga HSMM H3K4me2 rep2 H3K4me2 GSM646403
91 GSM646404_HSMM_H3K4me3_rep1.sga HSMM H3K4me3 rep1 H3K4me3 GSM646404
92 GSM646405_HSMM_H3K4me3_rep2.sga HSMM H3K4me3 rep2 H3K4me3 GSM646405
93 GSM646406_HSMM_H3K9ac_rep1.sga HSMM H3K9ac rep1 H3K9ac GSM646406
94 GSM646407_HSMM_H3K9ac_rep2.sga HSMM H3K9ac rep2 H3K9ac GSM646407
95 GSM646408_HSMM_H4K20me1_rep1.sga HSMM H4K20me1 rep1 H4K20me1 GSM646408
96 GSM646409_HSMM_H4K20me1_rep2.sga HSMM H4K20me1 rep2 H4K20me1 GSM646409
97 GSM646410_HSMM_WCE_rep1.sga HSMM WCE rep1 WCE GSM646410
98 GSM646411_HSMM_WCE_rep2.sga HSMM WCE rep2 WCE GSM646411
99 GSM646412_Huvec_CTCF_rep1.sga HUVEC CTCF rep1 CTCF GSM646412
100 GSM646413_Huvec_CTCF_rep2.sga HUVEC CTCF rep2 CTCF GSM646413
101 GSM646414_Huvec_H3K27ac_rep1.sga HUVEC H3K27ac rep1 H3K27ac GSM646414
102 GSM646415_Huvec_H3K27ac_rep2.sga HUVEC H3K27ac rep2 H3K27ac GSM646415
103 GSM646416_Huvec_H3K27me3_rep1.sga HUVEC H3K27me3 rep1 H3K27me3 GSM646416
104 GSM646417_Huvec_H3K27me3_rep2.sga HUVEC H3K27me3 rep2 H3K27me3 GSM646417
105 GSM646418_Huvec_H3K36me3_rep1.sga HUVEC H3K36me3 rep1 H3K36me3 GSM646418
106 GSM646419_Huvec_H3K36me3_rep2.sga HUVEC H3K36me3 rep2 H3K36me3 GSM646419
107 GSM646420_Huvec_H3K4me1_rep1.sga HUVEC H3K4me1 rep1 H3K4me1 GSM646420
108 GSM646421_Huvec_H3K4me1_rep2.sga HUVEC H3K4me1 rep2 H3K4me1 GSM646421
109 GSM646422_Huvec_H3K4me2_rep1.sga HUVEC H3K4me2 rep1 H3K4me2 GSM646422
110 GSM646423_Huvec_H3K4me2_rep2.sga HUVEC H3K4me2 rep2 H3K4me2 GSM646423
111 GSM646424_Huvec_H3K4me3_rep1.sga HUVEC H3K4me3 rep1 H3K4me3 GSM646424
112 GSM646425_Huvec_H3K4me3_rep2.sga HUVEC H3K4me3 rep2 H3K4me3 GSM646425
113 GSM646426_Huvec_H3K9ac_rep1.sga HUVEC H3K9ac rep1 H3K9ac GSM646426
114 GSM646427_Huvec_H3K9ac_rep2.sga HUVEC H3K9ac rep2 H3K9ac GSM646427
115 GSM646428_Huvec_H4K20me1_rep1.sga HUVEC H4K20me1 rep1 H4K20me1 GSM646428
116 GSM646429_Huvec_H4K20me1_rep2.sga HUVEC H4K20me1 rep2 H4K20me1 GSM646429
117 GSM646430_Huvec_WCE_rep1.sga HUVEC WCE rep1 WCE GSM646430
118 GSM646431_Huvec_WCE_rep2.sga HUVEC WCE rep2 WCE GSM646431
119 GSM646432_K562_CTCF_rep1.sga K562 CTCF rep1 CTCF GSM646432
120 GSM646433_K562_CTCF_rep2.sga K562 CTCF rep2 CTCF GSM646433
121 GSM646434_K562_H3K27ac_rep1.sga K562 H3K27ac rep1 H3K27ac GSM646434
122 GSM646435_K562_H3K27ac_rep2.sga K562 H3K27ac rep2 H3K27ac GSM646435
123 GSM646436_K562_H3K27me3_rep1.sga K562 H3K27me3 rep1 H3K27me3 GSM646436
124 GSM646437_K562_H3K27me3_rep2.sga K562 H3K27me3 rep2 H3K27me3 GSM646437
125 GSM646438_K562_H3K36me3_rep1.sga K562 H3K36me3 rep1 H3K36me3 GSM646438
126 GSM646439_K562_H3K36me3_rep2.sga K562 H3K36me3 rep2 H3K36me3 GSM646439
127 GSM646440_K562_H3K4me1_rep1.sga K562 H3K4me1 rep1 H3K4me1 GSM646440
128 GSM646441_K562_H3K4me1_rep2.sga K562 H3K4me1 rep2 H3K4me1 GSM646441
129 GSM646442_K562_H3K4me2_rep1.sga K562 H3K4me2 rep1 H3K4me2 GSM646442
130 GSM646443_K562_H3K4me2_rep2.sga K562 H3K4me2 rep2 H3K4me2 GSM646443
131 GSM646444_K562_H3K4me3_rep1.sga K562 H3K4me3 rep1 H3K4me3 GSM646444
132 GSM646445_K562_H3K4me3_rep2.sga K562 H3K4me3 rep2 H3K4me3 GSM646445
133 GSM646446_K562_H3K9ac_rep1.sga K562 H3K9ac rep1 H3K9ac GSM646446
134 GSM646447_K562_H3K9ac_rep2.sga K562 H3K9ac rep2 H3K9ac GSM646447
135 GSM646448_K562_H3K9me3_rep1.sga K562 H3K9me3 rep1 H3K9me3 GSM646448
136 GSM646449_K562_H3K9me3_rep2.sga K562 H3K9me3 rep2 H3K9me3 GSM646449
137 GSM646450_K562_H4K20me1_rep1.sga K562 H4K20me1 rep1 H4K20me1 GSM646450
138 GSM646451_K562_H4K20me1_rep2.sga K562 H4K20me1 rep2 H4K20me1 GSM646451
139 GSM646452_K562_WCE_rep1.sga K562 WCE rep1 WCE GSM646452
140 GSM646453_K562_WCE_rep2.sga K562 WCE rep2 WCE GSM646453
141 GSM646454_NHEK_CTCF_rep1.sga NHEK CTCF rep1 CTCF GSM646454
142 GSM646455_NHEK_CTCF_rep2.sga NHEK CTCF rep2 CTCF GSM646455
143 GSM646456_NHEK_H3K27ac_rep1.sga NHEK H3K27ac rep1 H3K27ac GSM646456
144 GSM646457_NHEK_H3K27ac_rep2.sga NHEK H3K27ac rep2 H3K27ac GSM646457
145 GSM646458_NHEK_H3K27me3_rep1.sga NHEK H3K27me3 rep1 H3K27me3 GSM646458
146 GSM646459_NHEK_H3K27me3_rep2.sga NHEK H3K27me3 rep2 H3K27me3 GSM646459
147 GSM646460_NHEK_H3K36me3_rep1.sga NHEK H3K36me3 rep1 H3K36me3 GSM646460
148 GSM646461_NHEK_H3K36me3_rep2.sga NHEK H3K36me3 rep2 H3K36me3 GSM646461
149 GSM646462_NHEK_H3K4me1_rep1.sga NHEK H3K4me1 rep1 H3K4me1 GSM646462
150 GSM646463_NHEK_H3K4me1_rep2.sga NHEK H3K4me1 rep2 H3K4me1 GSM646463
151 GSM646464_NHEK_H3K4me2_rep1.sga NHEK H3K4me2 rep1 H3K4me2 GSM646464
152 GSM646465_NHEK_H3K4me2_rep2.sga NHEK H3K4me2 rep2 H3K4me2 GSM646465
153 GSM646466_NHEK_H3K4me3_rep1.sga NHEK H3K4me3 rep1 H3K4me3 GSM646466
154 GSM646467_NHEK_H3K4me3_rep2.sga NHEK H3K4me3 rep2 H3K4me3 GSM646467
155 GSM646468_NHEK_H3K9ac_rep1.sga NHEK H3K9ac rep1 H3K9ac GSM646468
156 GSM646469_NHEK_H3K9ac_rep2.sga NHEK H3K9ac rep2 H3K9ac GSM646469
157 GSM646470_NHEK_H4K20me1_rep1.sga NHEK H4K20me1 rep1 H4K20me1 GSM646470
158 GSM646471_NHEK_H4K20me1_rep2.sga NHEK H4K20me1 rep2 H4K20me1 GSM646471
159 GSM646472_NHEK_WCE_rep1.sga NHEK WCE rep1 WCE GSM646472
160 GSM646473_NHEK_WCE_rep2.sga NHEK WCE rep2 WCE GSM646473
161 GSM646474_NHLF_CTCF_rep1.sga NHLF CTCF rep1 CTCF GSM646474
162 GSM646475_NHLF_CTCF_rep2.sga NHLF CTCF rep2 CTCF GSM646475
163 GSM646476_NHLF_H3K27ac_rep1.sga NHLF H3K27ac rep1 H3K27ac GSM646476
164 GSM646477_NHLF_H3K27ac_rep2.sga NHLF H3K27ac rep2 H3K27ac GSM646477
165 GSM646478_NHLF_H3K27me3_rep1.sga NHLF H3K27me3 rep1 H3K27me3 GSM646478
166 GSM646479_NHLF_H3K27me3_rep2.sga NHLF H3K27me3 rep2 H3K27me3 GSM646479
167 GSM646480_NHLF_H3K36me3_rep1.sga NHLF H3K36me3 rep1 H3K36me3 GSM646480
168 GSM646481_NHLF_H3K36me3_rep2.sga NHLF H3K36me3 rep2 H3K36me3 GSM646481
169 GSM646482_NHLF_H3K4me1_rep1.sga NHLF H3K4me1 rep1 H3K4me1 GSM646482
170 GSM646483_NHLF_H3K4me1_rep2.sga NHLF H3K4me1 rep2 H3K4me1 GSM646483
171 GSM646484_NHLF_H3K4me2_rep1.sga NHLF H3K4me2 rep1 H3K4me2 GSM646484
172 GSM646485_NHLF_H3K4me2_rep2.sga NHLF H3K4me2 rep2 H3K4me2 GSM646485
173 GSM646486_NHLF_H3K4me3_rep1.sga NHLF H3K4me3 rep1 H3K4me3 GSM646486
174 GSM646487_NHLF_H3K4me3_rep2.sga NHLF H3K4me3 rep2 H3K4me3 GSM646487
175 GSM646488_NHLF_H3K9ac_rep1.sga NHLF H3K9ac rep1 H3K9ac GSM646488
176 GSM646489_NHLF_H3K9ac_rep2.sga NHLF H3K9ac rep2 H3K9ac GSM646489
177 GSM646490_NHLF_H4K20me1_rep1.sga NHLF H4K20me1 rep1 H4K20me1 GSM646490
178 GSM646491_NHLF_H4K20me1_rep2.sga NHLF H4K20me1 rep2 H4K20me1 GSM646491
179 GSM646492_NHLF_WCE_rep1.sga NHLF WCE rep1 WCE GSM646492
180 GSM646493_NHLF_WCE_rep2.sga NHLF WCE rep2 WCE GSM646493


  1. Ernst J, Kheradpour P, Mikkelsen TS, Shoresh N et al.
    Mapping and analysis of chromatin state dynamics in nine human cell types. Nature. 2011 May 5;473(7345):43-9. PMID: 21441907

  2. GEO series GSE26320 Mapping and analysis of chromatin state dynamics in nine human cell types.