DNA methylation presents distinct binding sites for human transcription factors

Hu, Shaohui; Wan, Jun; Su, Yijing; Song, Qifeng; Zeng, Yue; Nguyen, Ha Nam; Shin, Jaehoon; Cox, Eric; Rho, Hee Sool; Woodard, Crystal; Xia, Shuli; Liu, Shuang; Lyu, Huibin; Ming, Guo Li; Wade, Herschel; Song, Hongjun; Qian, Jiang; Zhu, Heng

doi:10.7554/elife.00726

Cited by 309 publications

(318 citation statements)

References 47 publications

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“…Methylation of DNA has generally been associated with a reduction in transcription factor binding (36)(37)(38)(39); however, there is increasing evidence that mCpG-binding activity is widespread among specific transcription factor families, such as homeodomain transcription factors (40), of which PBX1 and HOXB9 are members. Our data provide the first evidence that suggests methylation of a specific CpG locus may induce the binding of alternative PBX-1-containing heterodimers to the EMSA probes, potentially adding a further layer of complexity to regulation by PBX-1.…”

Section: Discussionmentioning

confidence: 99%

PGC1α Promoter Methylation in Blood at 5–7 Years Predicts Adiposity From 9 to 14 Years (EarlyBird 50)

et al. 2014

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The early environment, acting via epigenetic processes, is associated with differential risk of cardiometabolic disease (CMD), which can be predicted by epigenetic marks in proxy tissues. However, such measurements at time points disparate from the health outcome or the environmental exposure may be confounded by intervening stochastic and environmental variation. To address this, we analyzed DNA methylation in the peroxisome proliferator–activated receptor γ coactivator 1α promoter in blood from 40 children (20 boys) collected annually between 5 and 14 years of age by pyrosequencing. Body composition was measured annually by dual X-ray absorptiometry, physical activity by accelerometry, and pubertal timing by age at peak high velocity. The effect of methylation on transcription factor binding was investigated by electrophoretic mobility shift assays. Seven cytosine guanine dinucleotide (CpG) loci were identified that showed no significant temporal change or association with leukocyte populations. Modeling using generalized estimating equations showed that methylation of four loci predicted adiposity up to 14 years independent of sex, age, pubertal timing, and activity. Methylation of one predictive locus modified binding of the proadipogenic pre–B-cell leukemia homeobox-1/homeobox 9 complex. These findings suggest that temporally stable CpG loci measured in childhood may have utility in predicting CMD risk.

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Section: Discussionmentioning

confidence: 99%

PGC1α Promoter Methylation in Blood at 5–7 Years Predicts Adiposity From 9 to 14 Years (EarlyBird 50)

et al. 2014

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“…The latter occurs on specific CG-rich DNA stretches termed ''CpG islands'' within the promoter region and interferes with normal transcription [117,118]. DNA methylation is maintained by DNA methyltransferase 1 (DNMT1), which predominantly methylates hemi-methylated DNA.…”

Section: Epigenetic Regulation Of the Rassfsmentioning

confidence: 99%

RASSF tumor suppressor gene family: Biological functions and regulation

et al. 2014

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a b s t r a c tGenetic changes through allelic loss and nucleic acid or protein modifications are the main contributors to loss of function of tumor suppressor proteins. In particular, epigenetic silencing of genes by promoter hypermethylation is associated with increased tumor severity and poor survival. The RASSF (Ras association domain family) family of proteins consists of 10 members, many of which are tumor suppressor proteins that undergo loss of expression through promoter methylation in numerous types of cancers such as leukemia, melanoma, breast, prostate, neck, lung, brain, colorectal and kidney cancers. In addition to their tumor suppressor function, RASSF proteins act as scaffolding agents in microtubule stability, regulate mitotic cell division, modulate apoptosis, control cell migration and cell adhesion, and modulate NFjB activity and the duration of inflammation. The ubiquitous functions of these proteins highlight their importance in numerous physiological pathways. In this review, we will focus on the biological roles of the RASSF family members and their regulation.

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“…Alternative methods are needed for capturing genome-wide binding data for many organisms. In vitro TFBS identification methods such as Protein Binding Microarrays (PBM) and High Throughput Systematic Evolution of Ligands by Exponential Enrichment (HT-SELEX) have achieved the highest throughput for deducing TF binding specificities in vitro [9][10][11] , but these methods use short synthetic oligonucleotides lacking secondary DNA modifications and genomic context, both important determinants of selective TF binding in vivo [12][13][14][15][16] . The DAP-seq technique 15 described here employs an in vitro-expressed affinitytagged TF in combination with high-throughput sequencing of a genomic DNA library, allowing for the generation of genome-wide binding site maps reflective of both local sequence context and DNA methylation status.…”

Section: Introductionmentioning

confidence: 99%

Mapping genome-wide transcription-factor binding sites using DAP-seq

Bartlett¹,

O’Malley²,

Huang³

et al. 2017

Nat Protoc

349

250

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In order to enable low-cost, high-throughput generation of cistrome and epicistrome maps for any organism, we developed DNA affinity purification sequencing (DAP-seq), a transcription factor (TF) binding site discovery assay that couples affinity-purified TFs with next-generation sequencing of a genomic DNA library. The method is fast, inexpensive, and more easily scaled than ChIP-seq. DNA libraries are constructed using native genomic DNA from any source of interest, preserving cell-and tissue-specific chemical modifications that are known to impact TF binding (such as DNA methylation) and providing increased specificity compared to in silico motif prediction methods such as protein binding microarrays (PBM) and systematic evolution of ligands by exponential enrichment (SELEX). The resulting DNA library is incubated with an affinity-tagged in vitro expressed TF, and TF-DNA complexes are purified using magnetic separation of the affinity tag. Bound genomic DNA is eluted from the TF and sequenced using next-generation sequencing. Sequence reads are mapped to a reference genome, identifying genome-wide binding locations for each TF assayed, from which sequence motifs can then be

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DNA methylation presents distinct binding sites for human transcription factors

Cited by 309 publications

References 47 publications

PGC1α Promoter Methylation in Blood at 5–7 Years Predicts Adiposity From 9 to 14 Years (EarlyBird 50)

PGC1α Promoter Methylation in Blood at 5–7 Years Predicts Adiposity From 9 to 14 Years (EarlyBird 50)

RASSF tumor suppressor gene family: Biological functions and regulation

Mapping genome-wide transcription-factor binding sites using DAP-seq

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