3D interactions with the growth hormone locus in cellular signalling and cancer-related pathways

in Journal of Molecular Endocrinology
Authors:
Lekha Jain Liggins Institute, University of Auckland, Auckland, New Zealand

Search for other papers by Lekha Jain in
Current site
Google Scholar
PubMed Close
,
Tayaza Fadason Liggins Institute, University of Auckland, Auckland, New Zealand

Search for other papers by Tayaza Fadason in
Current site
Google Scholar
PubMed Close
,
William Schierding Liggins Institute, University of Auckland, Auckland, New Zealand

Search for other papers by William Schierding in
Current site
Google Scholar
PubMed Close
,
Mark H Vickers Liggins Institute, University of Auckland, Auckland, New Zealand

Search for other papers by Mark H Vickers in
Current site
Google Scholar
PubMed Close
,
Justin M O’Sullivan Liggins Institute, University of Auckland, Auckland, New Zealand

Search for other papers by Justin M O’Sullivan in
Current site
Google Scholar
PubMed Close
, and
Jo K Perry Liggins Institute, University of Auckland, Auckland, New Zealand

Search for other papers by Jo K Perry in
Current site
Google Scholar
PubMed Close

Correspondence should be addressed to J K Perry or J M O’Sullivan: j.perry@auckland.ac.nz or justin.osullivan@auckland.ac.nz
DOI:
https://doi.org/10.1530/JME-20-0010
Volume/Issue:
Volume 64: Issue 4
Article Type:
Research Article
Page Range:
209–222
Online Publication Date:
May 2020
Copyright:
© 2020 Society for Endocrinology 2020
Restricted access
Rent on DeepDyve

Sign up for journal news

Growth hormone (GH) is a peptide hormone predominantly produced by the anterior pituitary and is essential for normal growth and metabolism. The GH locus contains five evolutionarily related genes under the control of an upstream locus control region that coordinates tissue-specific expression of these genes. Compromised GH signalling and genetic variation in these genes has been implicated in various disorders including cancer. We hypothesised that regulatory regions within the GH locus coordinate expression of a gene network that extends the impact of the GH locus control region. We used the CoDeS3D algorithm to analyse 529 common single nucleotide polymorphisms (SNPs) across the GH locus. This algorithm identifies colocalised Hi-C and eQTL associations to determine which SNPs are associated with a change in gene expression at loci that physically interact within the nucleus. One hundred and eighty-one common SNPs were identified that interacted with 292 eGenes across 48 different tissues. One hundred and forty-five eGenes were regulated in trans. eGenes were found to be enriched in GH/GHR-related cellular signalling pathways including MAPK, PI3K-AKT-mTOR, ERBB and insulin signalling, suggesting that these pathways may be co-regulated with GH signalling. Enrichment was also observed in the Wnt and Hippo signalling pathways and in pathways associated with hepatocellular, colorectal, breast and non-small cell lung carcinoma. Thirty-three eQTL SNPs identified in our study were found to be of regulatory importance in a genome-wide Survey of Regulatory Elements reporter screen. Our data suggest that the GH locus functions as a complex regulatory region that coordinates expression of numerous genes in cis and trans, many of which may be involved in modulating GH function in normal and disease states.

Supplementary Materials

    • Jain et al. Supplementary Figure 1: Correlation plot between SNP density across GH locus region and frequency of identified eGenes demonstrating that there was no correlation between them (R2=0.1).
    • Jain et al. Supplementary Figure 2: Correlation plot between number of samples present in GTEx per tissue and the number of cis-eQTLs in the respective tissue demonstrating a strong correlation between the two (R2=0.64).
    • Jain et al. Supplementary Figure 3: Distribution of topologically associating domain (TAD) structures with cis-eGenes (i.e. eGenes located <1 Mb from the SNP) and eGenes across chromosome 17 (both <1Mb and >1Mb apart from the SNPs). The Hi-C heat map was generated with the 3D Genome Browser using data from Rao et al42 for all the seven cell lines (GM12878, HMEC, KBM7, HUVEC, IMR90, K562 and NHEK). Tracks show TAD structures, the region containing the SNPs and identified eGenes. Blue and yellow bars represent different TAD regions.
    • Supplementary Data 1-a: List of common SNPs (dbSNP147) across GH gene locus (Chr17:62080000-61920000; GRCh37/hg19) used for analysis

Journal of Molecular Endocrinology is committed to supporting researchers in demonstrating the impact of their articles published in the journal.

The two types of article metrics we measure are (i) more traditional full-text views and pdf downloads, and (ii) Altmetric data, which shows the wider impact of articles in a range of non-traditional sources, such as social media.

More information is on the Reasons to publish page.

Sept 2018 onwards Past Year Past 30 Days
Full Text Views 557 64 0
PDF Downloads 358 15 0

 

  • Collapse
  • Expand
Online ISSN:
1479-6813
Print ISSN:
0952-5041
Copyright:
© 2020 Society for Endocrinology 2020
Page(s):
14
Article Type:
Research Article
Received Date:
17 Feb 2020
Accepted Date:
27 Feb 2020
Print Publication Date:
01 May 2020
Online Publication Date:
May 2020
Keywords:
growth hormone locus; GH1; genome; chromosome capture; cancer

  • Alfarano A, Indraccolo S, Circosta P, Minuzzo S, Vallario A, Zamarchi R, Fregonese A, Calderazzo F, Faldella A, Aragno M, et al. 1999 An alternatively spliced form of CD79b gene may account for altered B-cell receptor expression in B-chronic lymphocytic leukemia. Blood 93 2327–2335. (https://doi.org/10.1182/blood.v93.7.2327.407a08_2327_2335)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Ardlie KG, Deluca DS, Segrè AV, Sullivan TJ, Young TR, Gelfand ET, Trowbridge CA, Maller JB, Tukiainen T, Lek M, et al. 2015 Human genomics. The genotype-tissue expression (GTEx) pilot analysis: multitissue gene regulation in humans. Science 348 648–660. (https://doi.org/10.1126/science.1262110)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Bache SM & Wickham H 2016 magrittr: a forward-pipe operator for R. 12. (https://CRAN.R-project.org/package=magrittr)

  • Bartke A 2011 Growth hormone, insulin and aging: the benefits of endocrine defects. Experimental Gerontology 46 108–111. (https://doi.org/10.1016/j.exger.2010.08.020)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Berger P, Untergasser G, Hermann M, Hittmair A, Madersbacher S & Dirnhofer S 1999 The testis-specific expression pattern of the growth hormone/placental lactogen (GH/PL) gene cluster changes with malignancy. Human Pathology 30 1201–1206. (https://doi.org/10.1016/S0046-8177(99)90038-2)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Bonert VS & Melmed S 2017 Growth hormone. In The Pituitary, 4th ed., pp. 85–127. Elsevier. (https://doi.org/10.1016/B978-0-12-804169-7.00004-0)

  • Brittain AL, Basu R, Qian Y & Kopchick JJ 2017 Growth hormone and the epithelial-to-mesenchymal transition. Journal of Clinical Endocrinology and Metabolism 102 3662–3673. (https://doi.org/10.1210/jc.2017-01000)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Buniello A, Macarthur JAL, Cerezo M, Harris LW, Hayhurst J, Malangone C, McMahon A, Morales J, Mountjoy E, Sollis E, et al. 2019 The NHGRI-EBI GWAS catalog of published genome-wide association studies, targeted arrays and summary statistics 2019. Nucleic Acids Research 47 D1005–D1012. (https://doi.org/10.1093/nar/gky1120)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Carter-Su C, Schwartz J & Argetsinger LS 2016 Growth hormone signaling pathways. Growth Hormone and IGF Research 28 11–15. (https://doi.org/10.1016/j.ghir.2015.09.002)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Chen H, Levo M, Barinov L, Fujioka M, Jaynes JB & Gregor T 2018 Dynamic interplay between enhancer–promoter topology and gene activity. Nature Genetics 50 1296–1303. (https://doi.org/10.1038/s41588-018-0175-z)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Chesnokova V, Zonis S, Zhou C, Recouvreux MV, Ben-Shlomo A, Araki T, Barrett R, Workman M, Wawrowsky K, Ljubimov VA, et al. 2016 Growth hormone is permissive for neoplastic colon growth. PNAS 113 E3250–E3259. (https://doi.org/10.1073/pnas.1600561113)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Chhabra Y, Waters MJ & Brooks AJ 2011 Role of the growth hormone-IGF-1 axis in cancer. Expert Review of Endocrinology and Metabolism 6 71–84. (https://doi.org/10.1586/eem.10.73)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Chhabra Y, Wong HY, Nikolajsen LF, Steinocher H, Papadopulos A, Tunny KA, Meunier FA, Smith AG, Kragelund BB, Brooks AJ, et al. 2018 A growth hormone receptor SNP promotes lung cancer by impairment of SOCS2-mediated degradation. Oncogene 37 489–501. (https://doi.org/10.1038/onc.2017.352)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Ciabrelli F & Cavalli G 2015 Chromatin-driven behavior of topologically associating domains. Journal of Molecular Biology 427 608–625. (https://doi.org/10.1016/j.jmb.2014.09.013)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Clasen BF, Poulsen MM, Escande C, Pedersen SB, Møller N, Chini EN, Jessen N & Jørgensen JOL 2014 Growth hormone signaling in muscle and adipose tissue of obese human subjects: associations with measures of body composition and interaction with resveratrol treatment. Journal of Clinical Endocrinology and Metabolism 99 E2565–E2573. (https://doi.org/10.1210/jc.2014-2215)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Clayton PE, Banerjee I, Murray PG & Renehan AG 2011 Growth hormone, the insulin-like growth factor axis, insulin and cancer risk. Nature Reviews: Endocrinology 7 11–24. (https://doi.org/10.1038/nrendo.2010.171)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Dehkhoda F, Lee CMM, Medina J & Brooks AJ 2018 The growth hormone receptor: mechanism of receptor activation, cell signaling, and physiological aspects. Frontiers in Endocrinology 9 35. (https://doi.org/10.3389/fendo.2018.00035)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Dekker J, Marti-Renom MA & Mirny LA 2013 Exploring the three-dimensional organization of genomes: interpreting chromatin interaction data. Nature Reviews: Genetics 14 390–403. (https://doi.org/10.1038/nrg3454)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Duan K, Ezzat S, Asa SL & Mete O 2015 Pancreatic neuroendocrine tumors producing GHRH, GH, ghrelin, PTH, or PTHrP. In Pancreatic Neuroendocrine Neoplasms, pp. 125–139. Cham: Springer International Publishing. (https://doi.org/10.1007/978-3-319-17235-4_15)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Dunham I, Kundaje A, Aldred SF, Collins PJ, Davis CA, Doyle F, Epstein CB, Frietze S, Harrow J, Kaul R, et al. 2012 An integrated encyclopedia of DNA elements in the human genome. Nature 489 57–74. (https://doi.org/10.1038/nature11247)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Eijsbouts CQ, Burren OS, Newcombe PJ & Wallace C 2019 Fine mapping chromatin contacts in capture Hi-C data. BMC Genomics 20 77. (https://doi.org/10.1186/s12864-018-5314-5)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Fadason T, Ekblad C, Ingram JR, Schierding WS & O’Sullivan JM 2017 Physical interactions and expression quantitative traits loci identify regulatory connections for obesity and Type 2 diabetes associated SNPs. Frontiers in Genetics 8 150. (https://doi.org/10.3389/fgene.2017.00150)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Fishilevich S, Nudel R, Rappaport N, Hadar R, Plaschkes I, Iny Stein T, Rosen N, Kohn A, Twik M, Safran M, et al. 2017 GeneHancer: genome-wide integration of enhancers and target genes in GeneCards. Database 2017 bax028. (https://doi.org/10.1093/database/bax028)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Frick M, Bettstetter M, Bertz S, Schwarz-Furlan S, Hartmann A, Richter T, Lenze D, Hummel M, Dreyling M, Lenz G, et al. 2018 Mutational frequencies of CD79B and MYD88 vary greatly between primary testicular DLBCL and gastrointestinal DLBCL. Leukemia and Lymphoma 59 1260–1263. (https://doi.org/10.1080/10428194.2017.1370546)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Gadelha MR, Kasuki L, Lim DST & Fleseriu M 2019 Systemic complications of acromegaly and the impact of the current treatment landscape: an update. Endocrine Reviews 40 268–332. (https://doi.org/10.1210/er.2018-00115)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Ganguly E, Bock ME & Cattini PA 2015 Expression of placental members of the human growth hormone gene family is increased in response to sequential inhibition of DNA methylation and histone deacetylation. BioResearch Open Access 4 446–456. (https://doi.org/10.1089/biores.2015.0036)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Gibcus JH & Dekker J 2013 The hierarchy of the 3D genome. Molecular Cell 49 773–782. (https://doi.org/10.1016/j.molcel.2013.02.011)

  • Gómez-Rubio V 2017 ggplot2 – elegant graphics for data analysis (2nd edition) Journal of Statistical Software 77 3–5. (https://doi.org/10.18637/jss.v077.b02)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • González Alvarez R, Revol de Mendoza A, Esquivel Escobedo D, Corrales Félix G, Rodríguez Sánchez I, González V, Dávila G, Cao Q, de Jong P, Fu YX, et al. 2006 Growth hormone locus expands and diverges after the separation of new and old world monkeys. Gene 380 38–45. (https://doi.org/10.1016/j.gene.2006.05.017)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Grimm MOW, Lauer AA, Grösgen S, Thiel A, Lehmann J, Winkler J, Janitschke D, Herr C, Beisswenger C, Bals R, et al. 2019 Profiling of Alzheimer’s disease related genes in mild to moderate vitamin D hypovitaminosis. Journal of Nutritional Biochemistry 67 123–137. (https://doi.org/10.1016/j.jnutbio.2019.01.015)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Gu Z, Gu L, Eils R, Schlesner M & Brors B 2014 Circlize implements and enhances circular visualization in R. Bioinformatics 30 2811–2812. (https://doi.org/10.1093/bioinformatics/btu393)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Guevara-Aguirre J, Guevara A, Palacios I, Pérez M, Prócel P & Terán E 2018 GH and GHR signaling in human disease. Growth Hormone and IGF Research 38 34–38. (https://doi.org/10.1016/j.ghir.2017.12.006)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Hannon AM, Thompson CJ & Sherlock M 2017 Diabetes in patients with acromegaly. Current Diabetes Reports 17 8. (https://doi.org/10.1007/s11892-017-0838-7)

  • Hayashi AA & Proud CG 2007 The rapid activation of protein synthesis by growth hormone requires signaling through mTOR. American Journal of Physiology: Endocrinology and Metabolism 292 E1647–E1655. (https://doi.org/10.1152/ajpendo.00674.2006)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Ho Y, Tadevosyan A, Liebhaber SA & Cooke NE 2008 The juxtaposition of a promoter with a locus control region transcriptional domain activates gene expression. EMBO Reports 9 891–898. (https://doi.org/10.1038/embor.2008.126)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Kehrer-Sawatzki H, Mautner VF & Cooper DN 2017 Emerging genotype–phenotype relationships in patients with large NF1 deletions. Human Genetics 136 349–376. (https://doi.org/10.1007/s00439-017-1766-y)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Kikuchi M, Hara N, Hasegawa M, Miyashita A, Kuwano R, Ikeuchi T & Nakaya A 2019 Enhancer variants associated with Alzheimer’s disease affect gene expression via chromatin looping. BMC Medical Genomics 12 128. (https://doi.org/10.1186/s12920-019-0574-8)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Kim SJ 2003 Placental site trophoblastic tumour. Best Practice and Research: Clinical Obstetrics and Gynaecology 17 969–984. (https://doi.org/10.1016/S1521-6934(03)00095-6)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Kimura AP, Sizova D, Handwerger S, Cooke NE & Liebhaber SA 2007 Epigenetic activation of the human growth hormone gene cluster during placental cytotrophoblast differentiation. Molecular and Cellular Biology 27 6555–6568. (https://doi.org/10.1128/MCB.00273-07)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Kong S & Zhang Y 2019 Deciphering Hi-C: from 3D genome to function. Cell Biology and Toxicology 35 15–32. (https://doi.org/10.1007/s10565-018-09456-2)

  • Kong X, Wu W, Yuan Y, Pandey V, Wu Z, Lu X, Zhang W, Chen Y, Wu M, Zhang M, et al. 2016 Human growth hormone and human prolactin function as autocrine/paracrine promoters of progression of hepatocellular carcinoma. Oncotarget 7 29465–29479. (https://doi.org/10.18632/oncotarget.8781)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Lanctôt C, Cheutin T, Cremer M, Cavalli G & Cremer T 2007 Dynamic genome architecture in the nuclear space: regulation of gene expression in three dimensions. Nature Reviews: Genetics 8 104–115. (https://doi.org/10.1038/nrg2041)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Liao S, Vickers MH, Stanley JL, Baker PN & Perry JK 2018 Human placental growth hormone variant in pathological pregnancies. Endocrinology 159 2186–2198. (https://doi.org/10.1210/en.2018-00037)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Lieberman-Aiden E, Van Berkum NL, Williams L, Imakaev M, Ragoczy T, Telling A, Amit I, Lajoie BR, Sabo PJ, Dorschner MO, et al. 2009 Comprehensive mapping of long-range interactions reveals folding principles of the human genome. Science 326 289–293. (https://doi.org/10.1126/science.1181369)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Liu GY & Sabatini DM 2020 mTOR at the nexus of nutrition, growth, ageing and disease. Nature Reviews: Molecular Cell Biology In press. (https://doi.org/10.1038/s41580-019-0199-y)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Liu C, Zhang N, Yu H, Chen Y, Liang Y, Deng H & Zhang Z 2011 Proteomic analysis of human serum for Finding pathogenic factors and potential biomarkers in preeclampsia. Placenta 32 168–174. (https://doi.org/10.1016/j.placenta.2010.11.007)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Lizio M, Harshbarger J, Shimoji H, Severin J, Kasukawa T, Sahin S, Abugessaisa I, Fukuda S, Hori F, Ishikawa-Kato S, et al. 2015 Gateways to the FANTOM5 promoter level mammalian expression atlas. Genome Biology 16 22. (https://doi.org/10.1186/s13059-014-0560-6)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Lu M, Flanagan JU, Langley RJ, Hay MP & Perry JK 2019 Targeting growth hormone function: strategies and therapeutic applications. Signal Transduction and Targeted Therapy 4 3. (https://doi.org/10.1038/s41392-019-0036-y)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Männik J, Vaas P, Rull K, Teesalu P, Rebane T & Laan M 2010 Differential expression profile of growth hormone/chorionic somatomammotropin genes in placenta of small- and large-for-gestational-age newborns. Journal of Clinical Endocrinology and Metabolism 95 2433–2442. (https://doi.org/10.1210/jc.2010-0023)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Mirabello L, Yu K, Berndt SI, Burdett L, Wang Z, Chowdhury S, Teshome K, Uzoka A, Hutchinson A, Grotmol T, et al. 2011 A comprehensive candidate gene approach identifies genetic variation associated with osteosarcoma. BMC Cancer 11 209. (https://doi.org/10.1186/1471-2407-11-209)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Ohlsson R, Renkawitz R & Lobanenkov V 2001 CTCF is a uniquely versatile transcription regulator linked to epigenetics and disease. Trends in Genetics 17 520–527. (https://doi.org/10.1016/S0168-9525(01)02366-6)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Osmundsen AM, Keisler JL, Mark Taketo MM & Davis SW 2017 Canonical WNT signaling regulates the pituitary organizer and pituitary gland formation. Endocrinology 158 3339–3353. (https://doi.org/10.1210/en.2017-00581)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Pandey V, Perry JK, Mohankumar KM, Kong XJ, Liu SM, Wu ZS, Mitchell MD, Zhu T & Lobie PE 2008 Autocrine human growth hormone stimulates oncogenicity of endometrial carcinoma cells. Endocrinology 149 3909–3919. (https://doi.org/10.1210/en.2008-0286)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Pekic S, Stojanovic M & Popovic V 2017 Controversies in the risk of neoplasia in GH deficiency. Best Practice and Research: Clinical Endocrinology and Metabolism 31 35–47. (https://doi.org/10.1016/j.beem.2017.02.004)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Perry JK, Liu DX, Wu ZS, Zhu T & Lobie PE 2013 Growth hormone and cancer: an update on progress. Current Opinion in Endocrinology, Diabetes, and Obesity 20 307–313. (https://doi.org/10.1097/MED.0b013e328363183a)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Perry JK, Wu ZS, Mertani HC, Zhu T & Lobie PE 2017 Tumour-derived human growth hormone as a therapeutic target in oncology. Trends in Endocrinology and Metabolism 28 587–596. (https://doi.org/10.1016/j.tem.2017.05.003)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Rao SSP, Huntley MH, Durand NC, Stamenova EK, Bochkov ID, Robinson JT, Sanborn AL, Machol I, Omer AD, Lander ES, et al. 2014 A 3D map of the human genome at kilobase resolution reveals principles of chromatin looping. Cell 159 1665–1680. (https://doi.org/10.1016/j.cell.2014.11.021)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • . Raudvere U, Kolberg L, Kuzmin I, Arak T, Adler P, Peterson H & Vilo J 2019 g:Profiler: a web server for functional enrichment analysis and conversions of gene lists (2019 update) Nucleic Acids Research 47 W191–W198. (https://doi.org/10.1093/nar/gkz369)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Rotwein P & Chia DJ 2010 Gene regulation by growth hormone. Pediatric Nephrology 25 651–658. (https://doi.org/10.1007/s00467-009-1258-y)

  • Sanyal A, Lajoie BR, Jain G & Dekker J 2012 The long-range interaction landscape of gene promoters. Nature 489 109–113. (https://doi.org/10.1038/nature11279)

  • Saxton RA & Sabatini DM 2017 MTOR signaling in growth, metabolism, and disease. Cell 168 960–976. (https://doi.org/10.1016/j.cell.2017.02.004)

  • Schierding W & O’Sullivan JM 2015 Connecting SNPs in diabetes: a spatial analysis of meta-GWAS loci. Frontiers in Endocrinology 6 102. (https://doi.org/10.3389/fendo.2015.00102)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Schierding W, Antony J, Cutfield WS, Horsfield JA & O’Sullivan JM 2016 Intergenic GWAS SNPs are key components of the spatial and regulatory network for human growth. Human Molecular Genetics 25 3372–3382. (https://doi.org/10.1093/hmg/ddw165)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Schrader AMR, Jansen PM, Willemze R, Vermeer MH, Cleton-Jansen AM, Somers SF, Veelken H, Van Eijk R, Kraan W, Kersten MJ, et al. 2018 High prevalence of MYD88 and CD79B mutations in intravascular large B-cell lymphoma. Blood 131 2086–2089. (https://doi.org/10.1182/blood-2017-12-822817)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Simpson A, Petnga W, Macaulay VM, Weyer-Czernilofsky U & Bogenrieder T 2017 Insulin-like growth factor (IGF) pathway targeting in cancer: role of the IGF axis and opportunities for future combination studies. Targeted Oncology 12 571–597. (https://doi.org/10.1007/s11523-017-0514-5)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Splinter E, Heath H, Kooren J, Palstra RJ, Klous P, Grosveld F, Galjart N & De Laat W 2006 CTCF mediates long-range chromatin looping and local histone modification in the β-globin locus. Genes and Development 20 2349–2354. (https://doi.org/10.1101/gad.399506)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Su Y, Liebhaber SA & Cooke NE 1997 The human growth hormone locus control region supports pituitary- and placental-specific patterns of gene expression in transgenic mice. FASEB Journal 11 7902–7909. (https://doi.org/10.1074/jbc.275.11.7902)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Taciak B, Pruszynska I, Kiraga L, Bialasek M & Krol M 2018 Wnt signaling pathway in development and cancer. Journal of Physiology and Pharmacology 69 185– 196. (https://doi.org/10.26402/jpp.2018.2.07)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Tang Z, Luo OJ, Li X, Zheng M, Zhu JJ, Szalaj P, Trzaskoma P, Magalska A, Wlodarczyk J, Ruszczycki B, et al. 2015 CTCF-mediated human 3D genome architecture reveals chromatin topology for transcription. Cell 163 1611–1627. (https://doi.org/10.1016/j.cell.2015.11.024)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Tarnawski AS, Ahluwalia A, Gergely HM & Jones MK 2015 800 Expression and co-localization of IGF-1, its receptor and survivin in esophageal progenitor cells: implications for esophageal mucosal renewal, protection and healing. Gastroenterology 148 S-157. (https://doi.org/10.1016/S0016-5085(15)30529-1)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Tsai YC, Cooke NE & Liebhaber SA 2016 Long-range looping of a locus control region drives tissue-specific chromatin packing within a multigene cluster. Nucleic Acids Research 44 4651–4664. (https://doi.org/10.1093/nar/gkw090)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Ulianov SV, Khrameeva EE, Gavrilov AA, Flyamer IM, Kos P, Mikhaleva EA, Penin AA, Logacheva MD, Imakaev MV, Chertovich A, et al. 2016 Active chromatin and transcription play a key role in chromosome partitioning into topologically associating domains. Genome Research 26 70–84. (https://doi.org/10.1101/gr.196006.115)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • van Arensbergen J, Pagie L, FitzPatrick VD, de Haas M, Baltissen MP, Comoglio F, van der Weide RH, Teunissen H, Võsa U, Franke L, et al. 2019 High-throughput identification of human SNPs affecting regulatory element activity. Nature Genetics 51 1160–1169. (https://doi.org/10.1038/s41588-019-0455-2)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Vouyovitch CM, Perry JK, Liu DX, Bezin L, Vilain E, Diaz JJ, Lobie PE & Mertani HC 2016 WNT4 mediates the autocrine effects of growth hormone in mammary carcinoma cells. Endocrine-Related Cancer 23 571–585. (https://doi.org/10.1530/ERC-15-0528)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Wallis OC & Wallis M 2006 Evolution of growth hormone in primates: the GH gene clusters of the New World monkeys marmoset (Callithrix jacchus) and white-fronted capuchin (Cebus albifrons). Journal of Molecular Evolution 63 591–601. (https://doi.org/10.1007/s00239-006-0039-5)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Wang JJ, Chong QY, Sun XB, You ML, Pandey V, Chen YJ, Zhuang QS, Liu DX, Ma L, Wu ZS, et al. 2017 Autocrine hGH stimulates oncogenicity, epithelial-mesenchymal transition and cancer stem cell-like behavior in human colorectal carcinoma. Oncotarget 8 103900–103918. (https://doi.org/10.18632/oncotarget.21812)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Waters MJ 2016 The growth hormone receptor. Growth Hormone and IGF Research 28 6–10. (https://doi.org/10.1016/j.ghir.2015.06.001)

  • Zerbino DR, Achuthan P, Akanni W, Amode MR, Barrell D, Bhai J, Billis K, Cummins C, Gall A, Girón CG, et al. 2018 Ensembl 2018. Nucleic Acids Research 46 D754–D761. (https://doi.org/10.1093/nar/gkx1098)

    • PubMed
    • Search Google Scholar
    • Export Citation