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Architecture of the human regulatory network derived from ENCODE data.

Publication ,  Journal Article
Gerstein, MB; Kundaje, A; Hariharan, M; Landt, SG; Yan, K-K; Cheng, C; Mu, XJ; Khurana, E; Rozowsky, J; Alexander, R; Min, R; Alves, P; Fu, Y ...
Published in: Nature
September 6, 2012

Transcription factors bind in a combinatorial fashion to specify the on-and-off states of genes; the ensemble of these binding events forms a regulatory network, constituting the wiring diagram for a cell. To examine the principles of the human transcriptional regulatory network, we determined the genomic binding information of 119 transcription-related factors in over 450 distinct experiments. We found the combinatorial, co-association of transcription factors to be highly context specific: distinct combinations of factors bind at specific genomic locations. In particular, there are significant differences in the binding proximal and distal to genes. We organized all the transcription factor binding into a hierarchy and integrated it with other genomic information (for example, microRNA regulation), forming a dense meta-network. Factors at different levels have different properties; for instance, top-level transcription factors more strongly influence expression and middle-level ones co-regulate targets to mitigate information-flow bottlenecks. Moreover, these co-regulations give rise to many enriched network motifs (for example, noise-buffering feed-forward loops). Finally, more connected network components are under stronger selection and exhibit a greater degree of allele-specific activity (that is, differential binding to the two parental alleles). The regulatory information obtained in this study will be crucial for interpreting personal genome sequences and understanding basic principles of human biology and disease.

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Published In

Nature

DOI

EISSN

1476-4687

Publication Date

September 6, 2012

Volume

489

Issue

7414

Start / End Page

91 / 100

Location

England

Related Subject Headings

  • Transcription Initiation Site
  • Transcription Factors
  • Selection, Genetic
  • Regulatory Sequences, Nucleic Acid
  • RNA, Untranslated
  • Protein Interaction Maps
  • Polymorphism, Single Nucleotide
  • Phosphorylation
  • Organ Specificity
  • Molecular Sequence Annotation
 

Citation

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Gerstein, M. B., Kundaje, A., Hariharan, M., Landt, S. G., Yan, K.-K., Cheng, C., … Snyder, M. (2012). Architecture of the human regulatory network derived from ENCODE data. Nature, 489(7414), 91–100. https://doi.org/10.1038/nature11245
Gerstein, Mark B., Anshul Kundaje, Manoj Hariharan, Stephen G. Landt, Koon-Kiu Yan, Chao Cheng, Xinmeng Jasmine Mu, et al. “Architecture of the human regulatory network derived from ENCODE data.Nature 489, no. 7414 (September 6, 2012): 91–100. https://doi.org/10.1038/nature11245.
Gerstein MB, Kundaje A, Hariharan M, Landt SG, Yan K-K, Cheng C, et al. Architecture of the human regulatory network derived from ENCODE data. Nature. 2012 Sep 6;489(7414):91–100.
Gerstein, Mark B., et al. “Architecture of the human regulatory network derived from ENCODE data.Nature, vol. 489, no. 7414, Sept. 2012, pp. 91–100. Pubmed, doi:10.1038/nature11245.
Gerstein MB, Kundaje A, Hariharan M, Landt SG, Yan K-K, Cheng C, Mu XJ, Khurana E, Rozowsky J, Alexander R, Min R, Alves P, Abyzov A, Addleman N, Bhardwaj N, Boyle AP, Cayting P, Charos A, Chen DZ, Cheng Y, Clarke D, Eastman C, Euskirchen G, Frietze S, Fu Y, Gertz J, Grubert F, Harmanci A, Jain P, Kasowski M, Lacroute P, Leng JJ, Lian J, Monahan H, O’Geen H, Ouyang Z, Partridge EC, Patacsil D, Pauli F, Raha D, Ramirez L, Reddy TE, Reed B, Shi M, Slifer T, Wang J, Wu L, Yang X, Yip KY, Zilberman-Schapira G, Batzoglou S, Sidow A, Farnham PJ, Myers RM, Weissman SM, Snyder M. Architecture of the human regulatory network derived from ENCODE data. Nature. 2012 Sep 6;489(7414):91–100.
Journal cover image

Published In

Nature

DOI

EISSN

1476-4687

Publication Date

September 6, 2012

Volume

489

Issue

7414

Start / End Page

91 / 100

Location

England

Related Subject Headings

  • Transcription Initiation Site
  • Transcription Factors
  • Selection, Genetic
  • Regulatory Sequences, Nucleic Acid
  • RNA, Untranslated
  • Protein Interaction Maps
  • Polymorphism, Single Nucleotide
  • Phosphorylation
  • Organ Specificity
  • Molecular Sequence Annotation