ライフサイエンスコーパス: enhancer

1 lation of GR expression by a tissue-specific enhancer.

2 ely impairing the GR signaling axis via this enhancer.

3 em cell leukemia (SCL) gene driven by its 5' enhancer.

4 blood-brain barrier and acts as a cognitive enhancer.

5 s the N-terminal helix serves as an affinity enhancer.

6 lect the de novo acquisition of AML-specific enhancers.

7 , and considers the joint effect of multiple enhancers.

8 to be regulated by two nonredundant "shadow" enhancers.

9 with known cell type markers, promoters and enhancers.

10 en alpha- and beta-cells are concentrated in enhancers.

11 ERG enrichment at Dll4 promoter and multiple enhancers.

12 essential for LCL growth were linked to EBV enhancers.

13 ulatory sequences, including transcriptional enhancers.

14 cape of CRMs, to discriminate promoters from enhancers.

15 Thus, PcG targeting elements overlap with enhancers.

16 he other's binding at diverse sets of active enhancers.

17 stages and could thereby represent putative enhancers.

18 under the control of at least seven putative enhancers.

19 chromatin accessibility at temporal-specific enhancers.

20 marks of transcription, open chromatin, and enhancers.

21 and decreasing accessibility of early-acting enhancers.

22 F binding and the activity of the associated enhancers.

23 etal brain promoters and embryonic stem cell enhancers.

24 sk loci co-localize to recurrently activated enhancers.

25 ntegrator at immediate early genes and their enhancers.

26 encompassing 1,992 viral/cellular genes and enhancers.

27 echanism via conserved noncoding elements or enhancers.

28 These could serve as intronic splicing enhancers.

29 nd it accumulates in regions flanking active enhancers.

30 e genetically regulated CpGs are enriched in enhancers.

31 -CoR/SMRT-HDAC3 corepressor complex on these enhancers.

32 Here we identify AUTEN-99 (autophagy enhancer-99), which activates autophagy in cell cultures

33 consuming for large scale identification of enhancers across a variety of tissues under different di

34 Here, we report that the rainbow enhancers activate RGB cone-specific transcription of th

35 etyltransferases CBP/p300 to recruit Brd4 to enhancers activated during differentiation.

36 TAT3 is not the limiting factor for collagen enhancer activation in human lung fibroblasts.

37 cate the pioneer factor FOXA1 as a driver of enhancer activation in this system, a mechanism that ren

38 Enhancer-bound loop formation and enhancer activation of preformed loops together form mul

39 1 and zygotic Foxa at these CRMs to maintain enhancer activation.

40 s associated with suppression of LPS-induced enhancer activation.

41 l count association near CEBPA overlapped an enhancer active in common myeloid progenitors and influe

42 cus to a 5 kb region that overlaps a stretch-enhancer active in islets.

43 ion of DNA methylation targeted to candidate enhancers active in liver cells, enriched for the bindin

44 nstrated strong allele-specific promoter and enhancer activity and differential binding of HNF4alpha,

45 that alleles of rs7090445 have differential enhancer activity and influence RUNX3 binding.

46 found that Sox9-Brn2 and Isl1-Lhx3 regulate enhancer activity and NFIA expression in glial and neuro

47 tinct underlying DNA sequences and divergent enhancer activity as marked by histone 3 containing the

48 of sequences examined display p53-dependent enhancer activity during the DNA damage response.

49 r absence of tamoxifen, indicating divergent enhancer activity for tumors that develop in different e

50 leotide polymorphism, rs577676, which alters enhancer activity in a mouse atrial cell line and in emb

51 t on transcription factor (TF) occupancy and enhancer activity remains poorly understood.

52 Notably, we found that E93 controls enhancer activity through three different modalities, in

53 Loss of UTX leads to attenuated enhancer activity, characterized by reduced levels of H3

54 ided a quantitative metric of Tbx5-dependent enhancer activity, correlating with target gene expressi

55 nied by massive and recurrent alterations in enhancer activity.

56 enomic region surrounding the Eya1 locus for enhancer activity.

57 down reduces ARID5B expression and rs7090445 enhancer activity.

58 e effects, thereby buffering their impact on enhancer activity.

59 ssibility of an upstream genomic region with enhancer activity.

60 ets of features govern PPARgamma binding vs. enhancer activity.

61 to activation or inactivation of hundreds of enhancers along with drastic genome-wide reduction of HN

62 Misregulation of enhancer and promoter associated noncoding RNAs (ncRNAs)

63 urther promotes spatial clustering of MIR335 enhancer and promoter elements along with overexpression

64 nuclear interior and to juxtapose the Bcl11b enhancer and promoter into a single-loop domain.

65 nic mouse under the regulation of the Nkx2.5 enhancer and showed that neonatal Nkx2.5+ cardiomyoblast

66 d with reduced chromatin looping between the enhancer and the CUPID1 and CUPID2 bidirectional promote

67 Super-enhancers and broad H3K4me3 domains showed higher associ

68 he EWS-FLI1 fusion protein to tumor-specific enhancers and contributes to target gene activation.

69 uding promoting accessibility of late-acting enhancers and decreasing accessibility of early-acting e

70 TF)-dependence of ncRNA expression to define enhancers and enhancer-associated ncRNAs that are involv

71 discover three major co-regulation modes of enhancers and find defense-related genes often simultane

72 be trained on any tissue-specific dataset of enhancers and known functional variants and applied to p

73 educed chromatin accessibility at EBF2-bound enhancers and led to a decrease in basal and catecholami

74 ption is more bidirectional at newly evolved enhancers and promoter regions.

75 YY1 binds to active enhancers and promoter-proximal elements and forms dimer

76 mSWI/SNF assemblies, BAF and PBAF complexes, enhancers and promoters, respectively, suggesting that e

77 patterns of histone H3 Lys27 acetylation at enhancers and promoters, suggesting a cross-talk between

78 hromatin at lineage-specific transcriptional enhancers and promoters, which is mediated by pioneer tr

79 estricting chromatin accessibility at B cell enhancers and promoters.

80 A large number of distal enhancers and proximal promoters form enhancer-promoter

81 sense core promoter sequences, and that most enhancers and several families of repetitive elements ac

82 Our findings reveal a complex network of enhancers and TFs that dynamically cooperate to restore

83 Systematic mapping of functional enhancers and their biological contexts is required to u

84 in conformation analysis revealed that these enhancers and transcription factors form distinct archit

85 binds to transcription-primed promoters and enhancers, and to CTCF occupied, untranscribed chromatin

86 an with mechanistic studies on a beta-globin enhancer- and promoter-binding factor, GATA-1, the found

87 ental stages and brain-specific promoter and enhancer annotations.

88 al lineage and that corneal epithelial super enhancers are already marked as potential regulatory dom

89 In mammalian cells, active or primed enhancers are commonly marked by monomethylation of hist

90 Strikingly, Amphimedon enhancers are enriched in metazoan-specific microsynteni

91 y, our analyses revealed that most p53-bound enhancers are located within regions of inaccessible chr

92 Results suggest that hkCP enhancers are more likely to form multi-TSS interaction

93 associating domain (TAD) borders, while dCP enhancers are more often bound to one or two TSSs and ar

94 ed during patterning in the tissue where the enhancers are not induced, including at enhancers that a

95 Most pluripotency enhancers are selected later in the process and require

96 ge interactions between the Emu and 3'Ealpha enhancers are significantly diminished in the absence of

97 oncoproteins or mutations/variants in CEBPA enhancers are suggested in principal to reveal novel mec

98 and differentiation through transcriptional enhancer associate domain (TEAD) and runt-related transc

99 hese findings unveil Jmjd2c and G9a as novel enhancer-associated factors, and implicate Jmjd2c as a m

100 s showed strong Hi-C interaction enrichment, enhancer-associated histone modifications were evident,

101 the annotated lncRNA, IFNG-AS1, or one IFNG enhancer-associated lncRNA abrogates IFNG expression by

102 of ncRNA expression to define enhancers and enhancer-associated ncRNAs that are involved in a TF-dep

103 occupancy of architectural proteins, typical enhancer-associated proteins, and histone modifications,

104 The approach described here to identify enhancer-associated small insertion variants provides a

105 lation by Dve maintains expression from each enhancer at distinct homeostatic levels.

106 d to predict the genomic locations of active enhancers based on histone modifications, but the accura

107 ession (CAGE) demonstrate that promoters and enhancers, based on their expression profiles after stim

108 pecies petunia (Petunia hybrida), AP2B/BLIND ENHANCER (BEN) confines the C-function to the inner petu

109 the control of regulatory elements (Atoh1 3' enhancer/beta-globin basal promoter) to direct expressio

110 he DNA binding landscape of C/EBPbeta (CCAAT enhancer binding protein beta) without affecting its exp

111 CCAAT/enhancer binding proteins (C/EBPs) are expressed in vari

112 ith some nuclear proteins, i.e. the lymphoid enhancer-binding factor 1 (Lef1), histone H3, and Brahma

113 on of adipogenic transcription factors CCAAT/enhancer-binding protein alpha (C/EBPalpha), C/EBPbeta,

114 eracts with Tbeta4 and is recruited by CCAAT/enhancer-binding protein beta (C/EBPbeta) to discrete re

115 Ablation of CCAAT-enhancer-binding protein homologous protein (CHOP), the

116 (OC) precursors up-regulates c-Fos and CCAAT/enhancer-binding protein-alpha (C/EBPalpha), two critica

117 s often simultaneously regulated by multiple enhancers bound by different transcription factors.

118 Enhancer-bound loop formation and enhancer activation of

119 ermined accessibility was enriched at distal enhancers, but random monoallelically accessible (RAMA)

120 likelihood of a genetic variant deactivating enhancers by disrupting the binding of transcription fac

121 stically, IFN-gamma disassembled a subset of enhancers by inducing coordinate suppression of binding

122 CRISPR interference and activation at linked enhancers, by the presence of expression quantitative tr

123 ange chromatin interactions, suggesting that enhancers can influence the pause-initiation limit to re

124 md14-Enh by inducing enhancer components and enhancer chromatin accessibility.

125 istone modifications, we determine that both enhancer classes are enriched for RNA Polymerase II, CBP

126 e studies utilizing STARR-seq identified two enhancer classes in Drosophila that interact with differ

127 Related enhancers colocalize to the same microenvironments indep

128 Anemia activated Samd14-Enh by inducing enhancer components and enhancer chromatin accessibility

129 A large majority of new enhancers comprise transposable elements.

130 oma-specific BRD2/4-bound promoter and super-enhancer configuration.

131 CRISPR/Cas9 genomics revealed that super-enhancer constituents act cooperatively and facilitate D

132 in transgenic mice and fine-mapped separate enhancers controlling expression in joints versus growin

133 This promotes the binding of C/EBPbeta at enhancers controlling the expression of adipogenic targe

134 Thus, a GATA-2/anemia-regulated enhancer controls expression of an SAM domain protein th

135 nal analysis demonstrates that the Wap super-enhancer controls Ramp3, despite three separating CTCF s

136 sekeeping enhancers (hkCP) and developmental enhancers (dCP).

137 al disaccharide trehalose, a known autophagy enhancer, delays SG assembly and facilitates their prema

138 ere we demonstrate that CFIm functions as an enhancer-dependent activator of mRNA 3' processing.

139 sodium reduction and the addition of flavor enhancers did not constitute an obstacle to L. casei 01

140 inhibitor JQ1 preferentially inhibits super-enhancer-directed cotranscriptional pri-miRNA processing

141 mpletes complex bioinformatics tasks such as enhancer discovery and provides functions to integrate v

142 Here, we report that super-enhancers drive the biogenesis of master miRNAs crucial

143 Analysis of 54 Grh-responsive enhancers during development and upon wounding suggests

144 By analyzing enhancers during dorsal-ventral (DV) axis formation in t

145 A transcriptional enhancer element from the Mason-Pfizer monkey virus can

146 31746 mapped to a long-range neuron-specific enhancer element shown previously to regulate PCDH-alpha

147 -seq and ChIP-seq, that specific Runx1-bound enhancer elements critically modulate lineage-dependent

148 three-dimensional organization of the genes, enhancer elements, and transcription machinery plays an

149 events occur predominantly within regulatory enhancer elements.

150 ing with stage-specific activity of multiple enhancer elements.

151 pressed genes by suppressing the function of enhancers enriched for binding by transcription factor M

152 Additional EBV super-enhancer (ESE) targets included MCL1, IRF4, and EBF.

153 ns to genomic annotations (promoters, exons, enhancers, etc.).

154 Finally, characterization of enhancers exhibiting differential expression of enhancer

155 our characterization of a cell type-specific enhancer for the Wnt9b/beta-catenin target gene Fam19a5

156 atform that can identify stimulus-responsive enhancers for a target gene independent of stimulus expo

157 represent a new family of viral transduction enhancers for potential use in gene therapy.

158 in, and we show that paired sites buffer the enhancer from integration site-dependent effects on tran

159 n-dependent looping to reposition the Bcl11b enhancer from the lamina to the nuclear interior and to

160 ription response subclasses of promoters and enhancers from two different stimulations.

161 We show that two MEF2 sites in the enhancer function cooperatively due to bridging of the M

162 This highly sensitive phenotypic readout of enhancer function in a native genomic context reveals no

163 d by a similar cis mechanism to modulate LTR enhancer function in activating transcription of downstr

164 n "enhanceosome" and "smorgasbord" models of enhancer function, in which elements cooperate to bind c

165 the skull and long bones, showed that these enhancers function in an additive manner.

166 Here we present the Limb-Enhancer Genie (LEG), a collection of highly accurate, g

167 l3 (Kmt2c) and Mll4 (Kmt2d, Mll2), the major enhancer H3K4 monomethyltransferases.

168 The study of enhancers has been hampered by the scarcity of methods t

169 a role in splicing modulation, exonic splice enhancers have a lower SSM density before and after cont

170 p sequencing techniques in the recent years, enhancers have been systematically identified in such pr

171 with different core promoters: housekeeping enhancers (hkCP) and developmental enhancers (dCP).

172 Taken together, our results validate our enhancer identification pipeline and reveal that enhance

173 arch for factors that relocalized the Bcl11b enhancer identified a non-coding RNA named ThymoD (thymo

174 e of beta cells and is a component of active enhancers in both murine and human islets.

175 Identification of super-enhancers in DIPG provides insights toward the cell of o

176 Simultaneous deletion of these shadow enhancers in embryonic stem cells leads to impaired acti

177 ciated hypomethylation was enriched at super-enhancers in highly expressed genes critical for liver f

178 TPN6/PHB2, ANKRD11, and TNRC18 map to active enhancers in kidney cortex.

179 tigated the evolution of liver promoters and enhancers in six primate species using ChIP-seq (H3K27ac

180 highly accurate, genome-wide predictions of enhancers in the developing limb, available through a us

181 methods when predicting the target genes of enhancers in unseen samples, as evaluated by independent

182 e KLF1 from key erythroid gene promoters and enhancers in vivo.

183 expressed by altering OSK targeting, somatic-enhancer inactivation, and pluripotency enhancer selecti

184 atus, making computational identification of enhancers indispensable.

185 Thus, two enhancers integrate combinatorial transcription factor i

186 ression, indicating that long-range promoter-enhancer interaction mediated by CTCF plays important ro

187 reas the mode of repression of the slp1 PESE enhancer is transcription factor specific.

188 hmC and preferential enrichment at oncogenic enhancers is a novel regulatory mechanism in human pancr

189 By mapping changes in enhancer landscape and transcription factor occupancy (u

190 idization, we examined the epigenome and the enhancer landscape in X. tropicalis x X. laevis hybrid e

191 es results in signal-specific alterations in enhancer landscapes and associate with coordinated bindi

192 ranscription is a defining feature of active enhancers, linking transcription factor (TF) binding to

193 emonstrate that a highly conserved ERG-bound enhancer located upstream of HLX (which encodes a transc

194 re enhanced by natural variation at the drl2 enhancer locus, including reduced expression of the drl2

195 y separating the fetal globin genes from the enhancer (locus control region [LCR]).

196 ntitative trait loci, and by allele-specific enhancer loops in patient-derived primary cells.

197 MLV, suggesting MLV prefers smaller promoter-enhancer loops, whereas PB insertion encompasses larger

198 ion and indirect determination of the flavor enhancer maltol in foods and beverages.

199 toli and pregranulosa cells; however, active enhancers marked by H3K27ac were enriched proximal to on

200 Rainbow enhancers may represent a cis-regulatory mechanism to tu

201 vance in colon cancer modeling and implicate enhancer-mediated gene regulation as a principal tumor-s

202 onstrate a physiological role for intragenic enhancer-mediated transcription attenuation in cell fate

203 SPR/Cas9 was used to delete defined rhomboid enhancers mediating expression at each site of Spitz pro

204 longation and highlight that transcriptional enhancers might modulate the release of paused RNAPII vi

205 s unified TAD, both proximal and distal limb enhancers nevertheless continued to work independently o

206 ough a TLR4/nuclear factor kappa-light-chain-enhancer of activated B cells (NF-kappaB)/signal transdu

207 n levels of nuclear factor kappa-light-chain-enhancer of activated B cells and A20 were diminished in

208 kinase and nuclear factor kappa-light-chain-enhancer of activated B cells and negative regulators tu

209 phorylating nuclear factor kappa-light-chain-enhancer of activated B cells.

210 Our study introduces BA-DEG-BA as an enhancer of ADSC adipogenesis and suggests an integral i

211 bound to the H1-compacted promoter/proximal enhancer of the neuron-specific gene doublecortin (Dcx)

212 Here, we show enhancer of zeste homolog 2 (EZH2), an enzyme that catal

213 BP to promote activation of C/EBPbeta-primed enhancers of adipogenic genes.

214 ulin, DHA & EPA, vitamins B6, K1, and D3) as enhancers of calcium bioavailability according to recomm

215 No enhancers of the APIP promoter were found.

216 Sequence variation within enhancers plays a major role in both evolution and disea

217 Mll3/4 proteins leads to strong depletion of enhancer Pol II occupancy and eRNA synthesis, concomitan

218 and that the methylation levels at specific enhancers predict overall survival of AML patients.

219 o the action of a putative intronic splicing enhancer present in intron 25, which appeared to functio

220 Chromatin per se can stimulate efficient enhancer-promoter communication (EPC); however, the role

221 tmentalization to direct with high precision enhancer-promoter communication.

222 acterize a previously unknown liver-specific enhancer-promoter element in the wild-type AAV2 genome t

223 r complex to facilitate the establishment of enhancer-promoter interaction.

224 e that our method is effective in predicting enhancer-promoter interactions as compared to the state-

225 distal enhancers and proximal promoters form enhancer-promoter interactions to regulate target genes

226 Deletion of CTCF sites compromises enhancer-promoter interactions.

227 g sites or depletion of YY1 protein disrupts enhancer-promoter looping and gene expression.

228 ption factor Yin Yang 1 (YY1) contributes to enhancer-promoter structural interactions in a manner an

229 We found that strong viral enhancers/promoters placed in foamy viral vectors caused

230 rovirus/lentivirus vectors carrying the same enhancers/promoters, an effect not explained solely by f

231 ing mutations in PSENEN, encoding presenilin enhancer protein 2, in 6 unrelated patients and families

232 cular scaffold for the assembly of essential enhancer-protein complexes with an impact on timely gene

233 ding Panicum mosaic virus-like translational enhancer (PTE) and ribosome-binding 3' T-shaped structur

234 n factor EB or treatments with the autophagy enhancers rapamycin and Tat-Beclin-1 increased ureagenes

235 rs11708067 overlaps a predicted enhancer region in pancreatic islets.

236 f2 to an antioxidant response element in the enhancer region of the EDNRB gene.

237 e for the transcription factor ETS within an enhancer region.

238 DNA methylation is significantly altered at enhancer regions and that the methylation levels at spec

239 illustrate how sequences outside of minimal enhancer regions can evolve functionally through mechani

240 It occupies enhancer regions near lung cancer-associated genes, and

241 Chromatin rearrangements in enhancer regions occurred before the switch was complete

242 eq for islet-specific transcription factors, enhancer regions, and different histone marks were enric

243 Enhancers regulate gene expression through the binding o

244 that, in addition to regulating CCND1, this enhancer regulates two estrogen-regulated long noncoding

245 F binding sites, promoter-related marks, and enhancer-related histone modifications.

246 the Satb1-NuRD complex for binding to Pdcd1 enhancers, releasing Pdcd1 expression from Satb1-mediate

247 dinate with cell-type-specific TFs to select enhancer repertoires that enable differentiation during

248 show that in developing T cells, the Bcl11b enhancer repositioned from the lamina to the nuclear int

249 on of pancreatic cancer involves large-scale enhancer reprogramming by Foxa1, which activates transcr

250 Collectively, our study implicates enhancer reprogramming, FOXA1 upregulation, and a retrog

251 comprising IGF2 and a lineage-specific super-enhancer, resulting in high-level gene activation.

252 g putative targets, predicting TF responsive enhancers, revealing potential cofactors/collaborators a

253 nal global connectivity map of promoters and enhancers, revealing transcription-activity-linked genom

254 histone-, promoter upstream transcript- and enhancer RNA-loci.

255 We discuss the potential roles of enhancer RNAs (eRNAs) in early elongation and highlight

256 ancers exhibiting differential expression of enhancer RNAs pointed a central role for Kruppel-like fa

257 of lncRNA biology, such as the functions of enhancer RNAs, circular RNAs and chemical modifications

258 s and is associated with an archetypal super-enhancer (SE).

259 atic-enhancer inactivation, and pluripotency enhancer selection.

260 s/transcription factors in trans to hot spot enhancers serves as an effective biological strategy for

261 Large regulatory elements, so-called super-enhancers (SEs), are central to the maintenance of cance

262 However, enhancers/SEs mediating VSMC dysfunction remain uncharac

263 , CRISPR-Cas9-mediated deletion of candidate enhancers/SEs, targeting SEs with the bromodomain and ex

264 Promoters and enhancers share similar architectures and functions, and

265 Explaining these observations, enhancers show TF-dependent binding of the H3K27 demethy

266 e Drosophila embryo, we find that the poised enhancer signature is specifically generated during patt

267 that the mode of slp1 repression by Runt is enhancer specific, whereas the mode of repression of the

268 Shorter introns that contain enhancers splice early.

269 rough the donation of alternative promoters, enhancers, splice sites, and termination signals.

270 o Paired MEF2 sites are prevalent in cardiac enhancers, suggesting that this might be a common mechan

271 Finally, EBV super-enhancer-targeted IRF2 protected LCLs against Blimp1-med

272 by DNA methylation, including at an upstream enhancer that is protected by TET2, to allow Tet1 expres

273 the enhancers are not induced, including at enhancers that are known to be repressed by a transcript

274 blems, it could be useful to have salt taste enhancers that are not sodium based.

275 es accumulation of Pol II near promoters and enhancers that can best be explained by a rapid decrease

276 factors collaborate, they activate oncogenic enhancers that distinguish cancers from wounds.

277 overed extensive allelic interactions within enhancers that have opposite effects, thereby buffering

278 we identified hundreds of tissue-restricted enhancers that require the transcription factor (TF) CDX

279 e identified an emerging program of putative enhancers that revise H3.3 occupancy during regeneration

280 romatin remodeling complex to brown fat gene enhancers, thereby regulating chromatin accessibility.

281 otein complex associated with Wnt-responsive enhancers through T cell factors (TCF) and kept silent b

282 F sites are porous borders, allowing a super-enhancer to activate a secondary target.

283 ilizing and antifouling agent, as well as an enhancer to the mechanical and rejection properties of t

284 Three transcription factors act on these enhancers to determine cell-type specificity.

285 is required to activate brown adipose tissue enhancers to ensure thermogenic aptitude.

286 llel, we found that PAX6 binds promoters and enhancers to repress alternative islet cell genes includ

287 ncer identification pipeline and reveal that enhancers transcribed in breast cancer cells direct crit

288 We illustrate that TF-dependent enhancer transcription can illuminate components of TF-d

289 approach, we identified a novel Sertoli cell enhancer upstream of Wt1, and used it to drive expressio

290 We predict limb enhancers using a combination of >50 published limb-spec

291 resolving causal mutations in developmental enhancers, validated transcription-factor-binding sites

292 the physical proximity of a promoter and an enhancer, we constructed a three-dimensional global conn

293 Within this enhancer, we identified a single-nucleotide polymorphism

294 Genes harbouring hypomethylated enhancers were enriched for genes that change expression

295 owed that this intron functions as a genomic enhancer where glucocorticoid receptor binding regulates

296 fficient repair depends on the recombination enhancer, which tethers HMLalpha near the DSB.

297 An enhancer with amalgamated E-box and GATA motifs (+9.5) c

298 ugation process that co-localizes permeation enhancer with the protein.

299 5i induced a dramatic increase in H3K27ac at enhancers with an associated significant increase in tar

300 that CTCF binding sites are interwoven with enhancers within topologically associated domains (TADs)