Advertisement

Cell Biology and Toxicology

, Volume 34, Issue 6, pp 471–478 | Cite as

ZNF143 is a regulator of chromatin loop

  • Zi Wen
  • Zhi-Tao Huang
  • Ran Zhang
  • Cheng PengEmail author
Short Communication

Abstract

It is known that transcription factor ZNF143 frequently co-binds with CTCF-Cohesin complex in the anchor regions of chromatin loops. However, there is currently no genome-wide experiment to explore the functional roles of ZNF143 in chromatin loops. In this work, we used both computational and experimental analyses to investigate the regulatory effect of ZNF143 on chromatin loops. By jointly analyzing the ZNF143 and CTCF motifs underlying the isolated ZNF143-binding sites, ZNF143-CTCF co-binding sites and ZNF143-CTCF-RAD21 co-binding sites, our result shows that the ZNF143-CTCF-RAD21 co-binding sites are enriched with CTCF motifs but depleted of Znf143 motifs, implying that the CTCF but not ZNF143 may directly binds to the genome and thus ZNF143 may act as a cofactor instead of pioneer factor of ZNF143-CTCF-Cohesin complex. To explore the regulatory effect of ZNF143 on chromatin loops, we conducted siRNA experiment to knock down the expression level of ZNF143 in HEK293T cell line, and then performed in situ Hi-C on the negative control and ZNF143-silenced HEK293T cells. Comparison shows that the majority of chromatin loops are lost or at least weakened in the ZNF143-silenced HEK293T cells. However, a small proportion of chromatin loops are gained or strengthened, indicating the complicated roles of ZNF143 reduction in regulating chromatin loops. To further validate the loop analyses, we thoroughly investigated the chromatin loop changes between negative control and ZNF143-silenced cells by using aggregate peak analysis. The calculation shows that the lost and gained chromatin loops do undergo loop strength changes after ZNF143 silencing. Altogether, our work shows that ZNF143 can regulate chromatin loops by acting as a cofactor of CTCF-Cohesin complex, and knocking down ZNF143 expression level mainly eliminates or destabilizes chromatin loops.

Keywords

ZNF143 Chromatin loop Hi-C 3D genome 

Notes

Acknowledgements

Thanks to Prof. Gang Cao in Huazhong Agricultural University for providing experimental platform for cell culture, transfection, and western blotting.

Author contributions

Z.W. performed all data analyses, Z-T.H. performed in situ Hi-C experiments, and R.Z. performed cell culture, cell transfection, and western blotting. The work was conceived and designed by C.P.

Funding

This work was supported by the Natural Science Foundation of Hubei Province in China (Grant no. 2017CFB691) and Fundamental Research Funds for the Central Universities (Program no. 2662018JC032).

References

  1. Anno YN, Myslinski E, Ngondo-Mbongo RP, Krol A, Poch O, Lecompte O, et al. Genome-wide evidence for an essential role of the human Staf/ZNF143 transcription factor in bidirectional transcription. Nucleic Acids Res. 2011;39:3116–27.CrossRefPubMedGoogle Scholar
  2. Bailey TL, Boden M, Buske FA, Frith M, Grant CE, Clementi L, et al. MEME SUITE: tools for motif discovery and searching. Nucleic Acids Res. 2009;37:W202–8.CrossRefPubMedPubMedCentralGoogle Scholar
  3. Bailey SD, Zhang X, Desai K, Aid M, Corradin O, Cowper-Sal Lari R, et al. ZNF143 provides sequence specificity to secure chromatin interactions at gene promoters. Nat Commun. 2015;2:6186.CrossRefPubMedGoogle Scholar
  4. Bernstein BE, Birney E, Dunham I, Green ED, Gunter C, Snyder M. An integrated encyclopedia of DNA elements in the human genome. Nature. 2012;489:57–74.CrossRefGoogle Scholar
  5. Bonev B, Mendelson Cohen N, Szabo Q, Fritsch L, Papadopoulos GL, Lubling Y, et al. Multiscale 3D genome rewiring during mouse neural development. Cell. 2017;171:557–572.e24.Google Scholar
  6. Dekker J, Rippe K, Dekker M, Kleckner N. Capturing chromosome conformation. Science. 2002;295:1306–11.CrossRefPubMedGoogle Scholar
  7. Flavahan WA, Drier Y, Liau BB, Gillespie SM, Venteicher AS, Stemmer-Rachamimov AO, et al. Insulator dysfunction and oncogene activation in IDH mutant gliomas. Nature. 2016;529:110–4.CrossRefPubMedGoogle Scholar
  8. Grant CE, Bailey TL, Noble WS. FIMO: scanning for occurrences of a given motif. Bioinformatics. 2011;27:1017–8.CrossRefPubMedPubMedCentralGoogle Scholar
  9. Guo Y, Xu Q, Canzio D, Shou J, Li J, Gorkin DU, et al. CRISPR inversion of CTCF sites alters genome topology and enhancer/promoter function. Cell. 2015;162:900–10.CrossRefPubMedPubMedCentralGoogle Scholar
  10. Heidari N, Phanstiel DH, He C, Grubert F, Jahanbani F, Kasowski M, et al. Genome-wide map of regulatory interactions in the human genome. Genome Res. 2014;24:1905–17.CrossRefPubMedPubMedCentralGoogle Scholar
  11. Hnisz D, Day DS, Young RA. Insulated neighborhoods: structural and functional units of mammalian gene control. Cell. 2016a;167:1188–200.CrossRefPubMedPubMedCentralGoogle Scholar
  12. Hnisz D, Weintraub AS, Day DS, Valton AL, Bak RO, Li CH, et al. Activation of proto-oncogenes by disruption of chromosome neighborhoods. Science. 2016b;351:1454–8.CrossRefPubMedPubMedCentralGoogle Scholar
  13. Imakaev M, Fudenberg G, McCord RP, Naumova N, Goloborodko A, Lajoie BR, et al. Iterative correction of Hi-C data reveals hallmarks of chromosome organization. Nat Methods. 2012;9:999–1003.CrossRefPubMedPubMedCentralGoogle Scholar
  14. Krijger PH, Di Stefano B, de Wit E, Limone F, van Oevelen C, de Laat W, et al. Cell-of-origin-specific 3D genome structure acquired during somatic cell reprogramming. Cell Stem Cell. 2016;18:597–610.CrossRefPubMedPubMedCentralGoogle Scholar
  15. Kulakovskiy IV, Vorontsov IE, Yevshin IS, Sharipov RN, Fedorova AD, Rumynskiy EI, et al. HOCOMOCO: towards a complete collection of transcription factor binding models for human and mouse via large-scale ChIP-Seq analysis. Nucleic Acids Res. 2018;46:D252–9.CrossRefPubMedGoogle Scholar
  16. Li R, Liu Y, Hou Y, Gan J, Wu P, Li C. 3D genome and its disorganization in diseases. Cell Biol Toxicol. 2018.  https://doi.org/10.1007/s10565-018-9430-4.
  17. Lieberman-Aiden E, van Berkum NL, Williams L, Imakaev M, Ragoczy T, Telling A, et al. Comprehensive mapping of long-range interactions reveals folding principles of the human genome. Science. 2009;326:289–93.CrossRefPubMedPubMedCentralGoogle Scholar
  18. Ngondo-Mbongo RP, Myslinski E, Aster JC, Carbon P. Modulation of gene expression via overlapping binding sites exerted by ZNF143, Notch1 and THAP11. Nucleic Acids Res. 2013;41:4000–14.CrossRefPubMedPubMedCentralGoogle Scholar
  19. Nora EP, Goloborodko A, Valton AL, Gibcus JH, Uebersohn A, Abdennur N, et al. Targeted degradation of CTCF decouples local insulation of chromosome domains from genomic compartmentalization. Cell. 2017;169(930–944):e922.Google Scholar
  20. Rao SSP, Huntley MH, Durand NC, Stamenova EK, Bochkov ID, Robinson JT, et al. A 3D map of the human genome at kilobase resolution reveals principles of chromatin looping. Cell. 2014;159:1665–80.Google Scholar
  21. Rao SSP, Huang SC, Glenn St Hilaire B, Engreitz JM, Perez EM, Kieffer-Kwon KR, et al. Cohesin loss eliminates all loop domains. Cell. 2017;171:305–320.e24.Google Scholar
  22. Sanborn AL, Rao SSP, Huang SC, Durand NC, Huntley MH, Jewett AI, et al. Chromatin extrusion explains key features of loop and domain formation in wild-type and engineered genomes. Proc Natl Acad Sci U S A. 2015;112:E6456–65.Google Scholar
  23. Schwarzer W, Abdennur N, Goloborodko A, Pekowska A, Fudenberg G, Loe-Mie Y, et al. Two independent modes of chromatin organization revealed by cohesin removal. Nature. 2017;551:51–6.CrossRefPubMedPubMedCentralGoogle Scholar
  24. Szalaj P, Plewczynski D. Three-dimensional organization and dynamics of the genome. Cell Biol Toxicol. 2018.  https://doi.org/10.1007/s10565-018-9428-y.
  25. Tang Z, Luo OJ, Li X, Zheng M, Zhu JJ, Szalaj P, et al. CTCF-mediated human 3D genome architecture reveals chromatin topology for transcription. Cell. 2015;163:1611–27.CrossRefPubMedPubMedCentralGoogle Scholar
  26. Vinckevicius A, Parker JB, Chakravarti D. Genomic determinants of THAP11/ZNF143/HCFC1 complex recruitment to chromatin. Mol Cell Biol. 2015;35:4135–46.CrossRefPubMedPubMedCentralGoogle Scholar
  27. Wang XT, Cui W, Peng C. HiTAD: detecting the structural and functional hierarchies of topologically associating domains from chromatin interactions. Nucleic Acids Res. 2017;45:e163.CrossRefPubMedPubMedCentralGoogle Scholar
  28. Ye BY, Shen WL, Wang D, Li P, Zhang Z, Shi ML, et al. ZNF143 is involved in CTCF-mediated chromatin interactions by cooperation with cohesin and other partners. Mol Biol. 2016;+50:431–7.CrossRefGoogle Scholar
  29. Zhang K, Li N, Ainsworth RI, Wang W. Systematic identification of protein combinations mediating chromatin looping. Nat Commun. 2016;7:12249.CrossRefPubMedPubMedCentralGoogle Scholar

Copyright information

© Springer Nature B.V. 2018

Authors and Affiliations

  1. 1.Hubei Key Laboratory of Agricultural Bioinformatics, College of InformaticsHuazhong Agricultural UniversityWuhanChina
  2. 2.College of Life SciencesHebei Normal UniversityShijiazhuangChina

Personalised recommendations