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Unveiling the gene regulatory landscape in diseases through the identification of DNase I‑hypersensitive sites (Review)

  • Authors:
    • Ying Chen
    • Ailing Chen
  • View Affiliations

  • Published online on: July 31, 2019     https://doi.org/10.3892/br.2019.1233
  • Pages: 87-97
  • Copyright: © Chen et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

DNase I‑hypersensitive sites (DHSs) serve key roles in the regulation of gene transcription as markers of cis‑regulatory elements (CREs). Recent advances in next‑generation sequencing have enabled the genome‑wide location and annotation of DHSs in a variety of cells. Numerous studies have confirmed that DHSs are involved in several processes in cell fate decision and development. DHSs have also been indicated in cancer and inherited diseases as driver distal regulatory elements. Here, the definition of DHSs is reviewed, in addition to high‑throughput methods of DHS identification. Furthermore, the function of DHSs in gene expression is probed. The roles of DHSs in disease occurrence are also reviewed and discussed. Concomitant advances in the identification of essential roles of DHSs will assist in disclosing the underlying molecular mechanisms, supplementing gene transcription and enlarging the molecular basis of DHS‑related bioprocesses, phenotypes, distinct traits and diseases.

References

1 

Elgin SC: DNAase I-hypersensitive sites of chromatin. Cell. 27:413–415. 1981.

2 

Meisterernst M, Roy AL, Lieu HM and Roeder RG: Activation of class II gene transcription by regulatory factors is potentiated by a novel activity. Cell. 66:981–993. 1991.PubMed/NCBI View Article : Google Scholar

3 

Weintraub H and Groudine M: Chromosomal subunits in active genes have an altered conformation. Science. 193:848–856. 1976.PubMed/NCBI View Article : Google Scholar

4 

Felsenfeld G, Boyes J, Chung J, Clark D and Studitsky V: Chromatin structure and gene expression. Proc Natl Acad Sci USA. 93:9384–9388. 1996.PubMed/NCBI View Article : Google Scholar

5 

Wu C: The 5' ends of Drosophila heat shock genes in chromatin are hypersensitive to DNase I. Nature. 286:854–860. 1980.PubMed/NCBI View Article : Google Scholar

6 

Martinez-Balbas MA, Dey A, Rabindran SK, Ozato K and Wu C: Displacement of sequence-specific transcription factors from mitotic chromatin. Cell. 83:29–38. 1995.PubMed/NCBI View Article : Google Scholar

7 

Hebbes TR, Clayton AL, Thorne AW and Crane-Robinson C: Core histone hyperacetylation co-maps with generalized DNase I sensitivity in the chicken beta-globin chromosomal domain. EMBO J. 13:1823–1830. 1994.PubMed/NCBI View Article : Google Scholar

8 

Kleff S, Andrulis ED, Anderson CW and Sternglanz R: Identification of a gene encoding a yeast histone H4 acetyltransferase. J Biol Chem. 270:24674–24677. 1995.PubMed/NCBI View Article : Google Scholar

9 

Peterson CL and Tamkun JW: The SWI-SNF complex: A chromatin remodeling machine? Trends Biochem Sci. 20:143–146. 1995.PubMed/NCBI View Article : Google Scholar

10 

Roeder RG: The role of general initiation factors in transcription by RNA polymerase II. Trends Biochem Sci. 21:327–335. 1996.PubMed/NCBI View Article : Google Scholar

11 

Kim YJ, Bjorklund S, Li Y, Sayre MH and Kornberg RD: A multiprotein mediator of transcriptional activation and its interaction with the C-terminal repeat domain of RNA polymerase II. Cell. 77:599–608. 1994.PubMed/NCBI View Article : Google Scholar

12 

Koleske AJ and Young RA: An RNA polymerase II holoenzyme responsive to activators. Nature. 368:466–469. 1994.PubMed/NCBI View Article : Google Scholar

13 

Dynlacht BD, Hoey T and Tjian R: Isolation of coactivators associated with the TATA-binding protein that mediate transcriptional activation. Cell. 66:563–576. 1991.PubMed/NCBI View Article : Google Scholar

14 

Verrijzer CP and Tjian R: TAFs mediate transcriptional activation and promoter selectivity. Trends Biochem Sci. 21:338–342. 1996.PubMed/NCBI

15 

Lefevre P, Witham J, Lacroix CE, Cockerill PN and Bonifer C: The LPS-induced transcriptional upregulation of the chicken lysozyme locus involves CTCF eviction and noncoding RNA transcription. Mol Cell. 32:129–139. 2008.PubMed/NCBI View Article : Google Scholar

16 

Ishii H, Du H, Zhang Z, Henderson A, Sen R and Pazin MJ: Mi2beta shows chromatin enzyme specificity by erasing a DNase I-hypersensitive site established by ACF. J Biol Chem. 284:7533–7541. 2009.PubMed/NCBI View Article : Google Scholar

17 

Zeng WP and McFarland MM: Rapid and unambiguous detection of DNase I hypersensitive site in rare population of cells. PLoS One. 9(e85740)2014.PubMed/NCBI View Article : Google Scholar

18 

Trynka G, Sandor C, Han B, Xu H, Stranger BE, Liu XS and Raychaudhuri S: Chromatin marks identify critical cell types for fine mapping complex trait variants. Nat Genet. 45:124–130. 2013.PubMed/NCBI View Article : Google Scholar

19 

Frank CL, Manandhar D, Gordan R and Crawford GE: HDAC inhibitors cause site-specific chromatin remodeling at PU.1-bound enhancers in K562 cells. Epigenetics Chromatin. 9(15)2016.PubMed/NCBI View Article : Google Scholar

20 

Choi YC and Chae CB: DNA hypomethylation and germ cell-specific expression of testis-specific H2B histone gene. J Biol Chem. 266:20504–20511. 1991.PubMed/NCBI

21 

Ngo V, Gourdji D and Laverriere JN: Site-specific methylation of the rat prolactin and growth hormone promoters correlates with gene expression. Mol Cell Biol. 16:3245–3254. 1996.PubMed/NCBI View Article : Google Scholar

22 

Zhang T, Marand AP and Jiang J: PlantDHS: A database for DNase I hypersensitive sites in plants. Nucleic Acids Res. 44:D1148–D1153. 2016.PubMed/NCBI View Article : Google Scholar

23 

Deng T, Zhu ZI, Zhang S, Postnikov Y, Huang D, Horsch M, Furusawa T, Beckers J, Rozman J, Klingenspor M, et al: Functional compensation among HMGN variants modulates the DNase I hypersensitive sites at enhancers. Genome Res. 25:1295–1308. 2015.PubMed/NCBI View Article : Google Scholar

24 

Kodama Y, Nagaya S, Shinmyo A and Kato K: Mapping and characterization of DNase I hypersensitive sites in Arabidopsis chromatin. Plant Cell Physiol. 48:459–470. 2007.PubMed/NCBI View Article : Google Scholar

25 

Boyle AP, Davis S, Shulha HP, Meltzer P, Margulies EH, Weng Z, Furey TS and Crawford GE: High-resolution mapping and characterization of open chromatin across the genome. Cell. 132:311–322. 2008.PubMed/NCBI View Article : Google Scholar

26 

Crawford GE, Davis S, Scacheri PC, Renaud G, Halawi MJ, Erdos MR, Green R, Meltzer PS, Wolfsberg TG and Collins FS: DNase-chip: A high-resolution method to identify DNase I hypersensitive sites using tiled microarrays. Nat Methods. 3:503–509. 2006.PubMed/NCBI View Article : Google Scholar

27 

Crawford GE, Holt IE, Mullikin JC, Tai D, Blakesley R, Bouffard G, Young A, Masiello C, Green ED, Wolfsberg TG, et al: Identifying gene regulatory elements by genome-wide recovery of DNase hypersensitive sites. Proc Natl Acad Sci USA. 101:992–997. 2004.PubMed/NCBI View Article : Google Scholar

28 

Crawford GE, Holt IE, Whittle J, Webb BD, Tai D, Davis S, Margulies EH, Chen Y, Bernat JA, Ginsburg D, et al: Genome-wide mapping of DNase hypersensitive sites using massively parallel signature sequencing (MPSS). Genome Res. 16:123–131. 2006.PubMed/NCBI View Article : Google Scholar

29 

Thurman RE, Rynes E, Humbert R, Vierstra J, Maurano MT, Haugen E, Sheffield NC, Stergachis AB, Wang H, Vernot B, et al: The accessible chromatin landscape of the human genome. Nature. 489:75–82. 2012.PubMed/NCBI View Article : Google Scholar

30 

Vierstra J, Rynes E, Sandstrom R, Zhang M, Canfield T, Hansen RS, Stehling-Sun S, Sabo PJ, Byron R, Humbert R, et al: Mouse regulatory DNA landscapes reveal global principles of cis-regulatory evolution. Science. 346:1007–1012. 2014.PubMed/NCBI View Article : Google Scholar

31 

Morin A, Kwan T, Ge B, Letourneau L, Ban M, Tandre K, Caron M, Sandling JK, Carlsson J, Bourque G, et al: Immunoseq: The identification of functionally relevant variants through targeted capture and sequencing of active regulatory regions in human immune cells. BMC Med Genomics. 9(59)2016.PubMed/NCBI View Article : Google Scholar

32 

Cooper J, Ding Y, Song J and Zhao K: Genome-wide mapping of DNase I hypersensitive sites in rare cell populations using single-cell DNase sequencing. Nat Protoc. 12:2342–2354. 2017.PubMed/NCBI View Article : Google Scholar

33 

Jin W, Tang Q, Wan M, Cui K, Zhang Y, Ren G, Ni B, Sklar J, Przytycka TM, Childs R, et al: Genome-wide detection of DNase I hypersensitive sites in single cells and FFPE tissue samples. Nature. 528:142–146. 2015.PubMed/NCBI View Article : Google Scholar

34 

Lu F, Liu Y, Inoue A, Suzuki T, Zhao K and Zhang Y: Establishing chromatin regulatory landscape during mouse preimplantation development. Cell. 165:1375–1388. 2016.PubMed/NCBI View Article : Google Scholar

35 

Gross DS and Garrard WT: Nuclease hypersensitive sites in chromatin. Annu Rev Biochem. 57:159–197. 1988. View Article : Google Scholar

36 

Gaszner M and Felsenfeld G: Insulators: Exploiting transcriptional and epigenetic mechanisms. Nat Rev Genet. 7:703–713. 2006.PubMed/NCBI View Article : Google Scholar

37 

Li Q, Harju S and Peterson KR: Locus control regions: Coming of age at a decade plus. Trends Genet. 15:403–408. 1999.PubMed/NCBI View Article : Google Scholar

38 

Huang WY and Liew CC: A conserved GATA motif in a tissue-specific DNase I hypersensitive site of the cardiac alpha-myosin heavy chain gene. Biochem J. 325:47–51. 1997.PubMed/NCBI View Article : Google Scholar

39 

Bell O, Tiwari VK, Thoma NH and Schubeler D: Determinants and dynamics of genome accessibility. Nat Rev Genet. 12:554–564. 2011.PubMed/NCBI View Article : Google Scholar

40 

Pan Z, Lichtler AC and Upholt WB: DNase I hypersensitive sites in the chromatin of the chicken Msx2 gene differ in anterior and posterior limb mesenchyme, calvarial osteoblasts and embryonic fibroblasts. Biochem Mol Biol Int. 46:549–557. 1998.PubMed/NCBI

41 

Grünweller A, Purschke WG, Kügler S, Kruse C and Müller PK: Chicken vigilin gene: A distinctive pattern of hypersensitive sites is characteristic for its transcriptional activity. Biochem J. 326:601–607. 1997.PubMed/NCBI View Article : Google Scholar

42 

Heintzman ND, Stuart RK, Hon G, Fu Y, Ching CW, Hawkins RD, Barrera LO, Van Calcar S, Qu C, Ching KA, et al: Distinct and predictive chromatin signatures of transcriptional promoters and enhancers in the human genome. Nat Genet. 39:311–318. 2007.PubMed/NCBI View Article : Google Scholar

43 

Sheffield NC, Thurman RE, Song L, Safi A, Stamatoyannopoulos JA, Lenhard B, Crawford GE and Furey TS: Patterns of regulatory activity across diverse human cell types predict tissue identity, transcription factor binding, and long-range interactions. Genome Res. 23:777–788. 2013.PubMed/NCBI View Article : Google Scholar

44 

Liu Y, Ding D, Liu H and Sun X: The accessible chromatin landscape during conversion of human embryonic stem cells to trophoblast by bone morphogenetic protein 4. Biol Reprod. 96:1267–1278. 2017.PubMed/NCBI View Article : Google Scholar

45 

Dong X, Wang X, Zhang F and Tian W: Genome-wide identification of regulatory sequences undergoing accelerated evolution in the human genome. Mol Biol Evol. 33:2565–2575. 2016.PubMed/NCBI View Article : Google Scholar

46 

Mokry M, Harakalova M, Asselbergs FW, de Bakker PI and Nieuwenhuis EE: Extensive association of common disease variants with regulatory sequence. PLoS One. 11(e0165893)2016.PubMed/NCBI View Article : Google Scholar

47 

D'Antonio M and Ciccarelli FD: Integrated analysis of recurrent properties of cancer genes to identify novel drivers. Genome Biol. 14(R52)2013.PubMed/NCBI View Article : Google Scholar

48 

Perera D, Poulos RC, Shah A, Beck D, Pimanda JE and Wong JW: Differential DNA repair underlies mutation hotspots at active promoters in cancer genomes. Nature. 532:259–263. 2016.PubMed/NCBI View Article : Google Scholar

49 

Peterson RE, Cai N, Bigdeli TB, Li Y, Reimers M, Nikulova A, Webb BT, Bacanu SA, Riley BP, Flint J and Kendler KS: The genetic architecture of major depressive disorder in han chinese women. JAMA Psychiatry. 74:162–168. 2017.PubMed/NCBI View Article : Google Scholar

50 

Turner TN, Hormozdiari F, Duyzend MH, McClymont SA, Hook PW, Iossifov I, Raja A, Baker C, Hoekzema K, Stessman HA, et al: Genome sequencing of autism-affected families reveals disruption of putative noncoding regulatory DNA. Am J Hum Genet. 98:58–74. 2016.PubMed/NCBI View Article : Google Scholar

51 

Yuen RK, Merico D, Cao H, Pellecchia G, Alipanahi B, Thiruvahindrapuram B, Tong X, Sun Y, Cao D, Zhang T, et al: Genome-wide characteristics of de novo mutations in autism. NPJ Genom Med. 1:160271–1602710. 2016.PubMed/NCBI View Article : Google Scholar

52 

Wang K, Sturt-Gillespie B, Hittle JC, Macdonald D, Chan GK, Yen TJ and Liu ST: Thyroid hormone receptor interacting protein 13 (TRIP13) AAA-ATPase is a novel mitotic checkpoint-silencing protein. J Biol Chem. 289:23928–23937. 2014.PubMed/NCBI View Article : Google Scholar

53 

Rafnar T, Sulem P, Stacey SN, Geller F, Gudmundsson J, Sigurdsson A, Jakobsdottir M, Helgadottir H, Thorlacius S, Aben KK, et al: Sequence variants at the TERT-CLPTM1L locus associate with many cancer types. Nat Genet. 41:221–227. 2009.PubMed/NCBI View Article : Google Scholar

54 

Abdelzaher E and MostafaM F: Lysophosphatidylcholine acyltransferase 1 (LPCAT1) upregulation in breast carcinoma contributes to tumor progression and predicts early tumor recurrence. Tumour Biol. 36:5473–5483. 2015.PubMed/NCBI View Article : Google Scholar

55 

D Antonio M, Weghorn D, D Antonio-Chronowska A, Coulet F, Olson KM, DeBoever C, Drees F, Arias A, Alakus H, Richardson AL, et al: Identifying DNase I hypersensitive sites as driver distal regulatory elements in breast cancer. Nat Commun. 8(436)2017.PubMed/NCBI View Article : Google Scholar

56 

Guo X, Long J, Zeng C, Michailidou K, Ghoussaini M, Bolla MK, Wang Q, Milne RL, Shu XO, Cai Q, et al: Fine-scale mapping of the 4q24 locus identifies two independent loci associated with breast cancer risk. Cancer Epidemiol Biomarkers Prev. 24:1680–1691. 2015.PubMed/NCBI View Article : Google Scholar

57 

Jiang T, Du F, Qin N, Lu Q, Dai J, Shen H and Hu Z: Systematical analyses of variants in DNase I hypersensitive sites to identify hepatocellular carcinoma susceptibility loci in a Chinese population. J Gastroenterol Hepatol. 32:1887–1894. 2017.PubMed/NCBI View Article : Google Scholar

58 

Nakaoka H, Gurumurthy A, Hayano T, Ahmadloo S, Omer WH, Yoshihara K, Yamamoto A, Kurose K, Enomoto T, Akira S, et al: Allelic imbalance in regulation of ANRIL through chromatin interaction at 9p21 endometriosis risk locus. PLoS Genet. 12(e1005893)2016.PubMed/NCBI View Article : Google Scholar

59 

He HH, Meyer CA, Chen MW, Jordan VC, Brown M and Liu XS: Differential DNase I hypersensitivity reveals factor-dependent chromatin dynamics. Genome Res. 22:1015–1025. 2012.PubMed/NCBI View Article : Google Scholar

60 

Wei X, Yu L, Jin X, Song L, Lv Y and Han Y: Identification of open chromosomal regions and key genes in prostate cancer via integrated analysis of DNase-seq and RNA-seq data. Mol Med Rep. 18:2245–2252. 2018.PubMed/NCBI View Article : Google Scholar

61 

Kallioniemi A: Bone morphogenetic protein 4-a fascinating regulator of cancer cell behavior. Cancer Genet. 205:267–277. 2012.PubMed/NCBI View Article : Google Scholar

62 

Ampuja M, Rantapero T, Rodriguez-Martinez A, Palmroth M, Alarmo EL, Nykter M and Kallioniemi A: Integrated RNA-seq and DNase-seq analyses identify phenotype-specific BMP4 signaling in breast cancer. BMC Genomics. 18(68)2017.PubMed/NCBI View Article : Google Scholar

63 

de Boer B, Prick J, Pruis MG, Keane P, Imperato MR, Jaques J, Brouwers-Vos AZ, Hogeling SM, Woolthuis CM, Nijk MT, et al: Prospective isolation and characterization of genetically and functionally distinct AML subclones. Cancer Cell. 34:674–689. 2018.PubMed/NCBI View Article : Google Scholar

64 

Stergachis AB, Neph S, Reynolds A, Humbert R, Miller B, Paige SL, Vernot B, Cheng JB, Thurman RE, Sandstrom R, et al: Developmental fate and cellular maturity encoded in human regulatory DNA landscapes. Cell. 154:888–903. 2013.PubMed/NCBI View Article : Google Scholar

65 

Wei C and Dong X, Lu H, Tong F, Chen L, Zhang R, Dong J, Hu Y, Wu G and Dong X: LPCAT1 promotes brain metastasis of lung adenocarcinoma by up-regulating PI3K/AKT/MYC pathway. J Exp Clin Cancer Res. 38(95)2019.PubMed/NCBI View Article : Google Scholar

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APA
Chen, Y., & Chen, Y. (2019). Unveiling the gene regulatory landscape in diseases through the identification of DNase I‑hypersensitive sites (Review). Biomedical Reports, 11, 87-97. https://doi.org/10.3892/br.2019.1233
MLA
Chen, Y., Chen, A."Unveiling the gene regulatory landscape in diseases through the identification of DNase I‑hypersensitive sites (Review)". Biomedical Reports 11.3 (2019): 87-97.
Chicago
Chen, Y., Chen, A."Unveiling the gene regulatory landscape in diseases through the identification of DNase I‑hypersensitive sites (Review)". Biomedical Reports 11, no. 3 (2019): 87-97. https://doi.org/10.3892/br.2019.1233