ARID1B, a molecular suppressor of erythropoiesis, is essential for the prevention of Monge’s disease
2
조회
0
다운로드
0
인용
0
참고문헌
초록
At high altitude Andean region, hypoxia-induced excessive erythrocytosis (EE) is the defining feature of Monge’s disease or chronic mountain sickness (CMS). At the same altitude, resides a population that has developed adaptive mechanism(s) to constrain this hypoxic response (non-CMS). In this study, we utilized an in vitro induced pluripotent stem cell model system to study both populations using genomic and molecular approaches. Our whole genome analysis of the two groups identified differential SNPs between the CMS and non-CMS subjects in the ARID1B region. Under hypoxia, the expression levels of ARID1B significantly increased in the non-CMS cells but decreased in the CMS cells. At the molecular level, ARID1B knockdown (KD) in non-CMS cells increased the levels of the transcriptional regulator GATA1 by 3-fold and RBC levels by 100-fold under hypoxia. ARID1B KD in nonCMS cells led to increased proliferation and EPO sensitivity by lowering p53 levels and decreasing apoptosis through GATA1 mediation. Interestingly, under hypoxia ARID1B showed an epigenetic role, altering the chromatin states of erythroid genes. Indeed, combined Real-time PCR and ATAC-Seq results showed that ARID1B modulates the expression of GATA1 and p53 and chromatin accessibility at GATA1/p53 target genes. We conclude that ARID1B is a novel erythroid regulator under hypoxia that controls various aspects of erythropoiesis in high-altitude dwellers.
Abstract
At high altitude Andean region, hypoxia-induced excessive erythrocytosis (EE) is the defining feature of Monge’s disease or chronic mountain sickness (CMS). At the same altitude, resides a population that has developed adaptive mechanism(s) to constrain this hypoxic response (non-CMS). In this study, we utilized an in vitro induced pluripotent stem cell model system to study both populations using genomic and molecular approaches. Our whole genome analysis of the two groups identified differential SNPs between the CMS and non-CMS subjects in the ARID1B region. Under hypoxia, the expression levels of ARID1B significantly increased in the non-CMS cells but decreased in the CMS cells. At the molecular level, ARID1B knockdown (KD) in non-CMS cells increased the levels of the transcriptional regulator GATA1 by 3-fold and RBC levels by 100-fold under hypoxia. ARID1B KD in nonCMS cells led to increased proliferation and EPO sensitivity by lowering p53 levels and decreasing apoptosis through GATA1 mediation. Interestingly, under hypoxia ARID1B showed an epigenetic role, altering the chromatin states of erythroid genes. Indeed, combined Real-time PCR and ATAC-Seq results showed that ARID1B modulates the expression of GATA1 and p53 and chromatin accessibility at GATA1/p53 target genes. We conclude that ARID1B is a novel erythroid regulator under hypoxia that controls various aspects of erythropoiesis in high-altitude dwellers.
참고문헌 (52)
- Azad, P., "Senp1 drives hypoxia-induced polycythemia via GATA1 and Bcl-xL in subjects with Monge’s disease", J. Exp. Med, 213, pp.2729~2744 (2016)
- Monge, C. C., "Chronic mountain-sickness", Johns. Hopkins Med. J, 139, pp.87~89 (1976)
- Stobdan, T., "New insights into the genetic basis of Monge’s disease and adaptation to high-altitude", Mol. Biol. Evol, 34, pp.3154~3168 (2017)
- Villafuerte, F. C., "Chronic mountain sickness: Clinical aspects, etiology, management, and treatment", High. Alt. Med. Biol, 17, pp.61~69 (2016)
- Zhou, D., "Whole-genome sequencing uncovers the genetic basis of chronic mountain sickness in Andean highlanders", Am. J. Hum. Genet, 93, pp.452~462 (2013)
- Azad, P., "High-altitude adaptation in humans : From genomics to integrative physiology", J. Mol. Med, 95, pp.1269~1282 (2017)
- Beall, C. M., "Andean, Tibetan, and Ethiopian patterns of adaptation to highaltitude hypoxia", Integr. Comp. Biol, 46, pp.18~24 (2006)
- Bigham, A., "Identifying signatures of natural selection in tibetan and andean populations using dense genome scan data", Plos Genet, 6, pp.e1001116~ (2010)
- Dainiak, N., "Erythropoietin and the polycythemia of high-altitude dwellers", Adv. Exp. Med. Biol, 271, pp.17~21 (1989)
- Naeije, R., "Pulmonary hypertension and chronic mountain sickness", High. Alt. Med. Biol, 14, pp.117~125 (2013)
- De Andrade, T., "Expression of new red cell-related genes in erythroid differentiation", Biochem. Genet, 48, pp.164~171 (2010)
- de Andrade, T. G., "Identification of novel candidate genes for globin regulation in erythroid cells containing large deletions of the human beta-globin gene cluster", Blood Cell. Mol. Dis, 37, pp.82~90 (2006)
- Santen, G. W., "The ARID1B phenotype:what we have learned so far", Am. J. Med. Genet. Part C, 166C, pp.276~289 (2014)
- Lin, J., "ARID1B : From the garden of Eden to the Sahara", J. Thorac. Cardiovasc. Surg, 155, pp.e193~e194 (2018)
- Lu, C., "SWI", SNF complex in cancer, 2017, pp.49, 178~179
- Prasad, P., "The roles of SNF2", SWI2 nucleosome remodeling enzymes in blood cell differentiation and leukemia, 2015, pp.2015, 347571~
- Zhao, H. W., "Altered iPSC-derived neurons’ sodium channel properties in subjects with Monge’s disease", Neuroscience, 288, pp.187~199 (2015)
- Kobari, L., "Human induced pluripotent stem cells can reach complete terminal maturation : in vivo and in vitro evidence in the erythropoietic differentiation model", Haematologica, 97, pp.1795~1803 (2012)
- Lee, K. S., "JNK", FOXO-mediated neuronal expression of fly homologue of peroxiredoxin II reduces oxidative stress and extends life span, 2009, pp.284, 29454~29461
- Buenrostro, J. D., "Transposition of native chromatin for fast and sensitive epigenomic profiling of open chromatin, DNA-binding proteins and nucleosome position", Nat. Methods, 10, pp.1213~1218 (2013)
- Ross-Innes, C. S., "Differential oestrogen receptor binding is associated with clinical outcome in breast cancer", Nature, 481, pp.389~393 (2012)
- Yu, G., "ChIPseeker : An R", Bioconductor package for ChIP peak annotation, comparison and visualization, 2015, pp.31, 2382~2383
- Lee, S., "plyranges : A grammar of genomic data transformation", Genome Biol, 20, pp.4~ (2019)
- van Heeringen, S. J., "GimmeMotifs : A de novo motif prediction pipeline for ChIP-sequencing experiments", Bioinformatics, 27, pp.270~271 (2011)
- Heinz, S., "Simple combinations of lineage-determining transcription factors prime cis-regulatory elements required for macrophage and B cell identities", Mol. Cell, 38, pp.576~589 (2010)
- Welch, R. P., "ChIP-Enrich : Gene set enrichment testing for ChIP-seq data", Nucleic Acids Res, 42, pp.e105~ (2014)
- Chen, E. Y., "Enrichr : Interactive and collaborative HTML5 gene list enrichment analysis tool", BMC Bioinforma, 14, pp.128~ (2013)
- Kuleshov, M. V., "Enrichr : A comprehensive gene set enrichment analysis web server 2016 update", Nucleic Acids Res, 44, pp.W90~W97 (2016)
- Sloan, C. A., "ENCODE data at the ENCODE portal", Nucleic Acids Res, 44, pp.D726~D732 (2016)
- Li, Z., "Identification of transcription factor binding sites using ATAC-seq", Genome Biol, 20, pp.45~ (2019)
- Kulakovskiy, I. V., "HOCOMOCO : Towards a complete collection of transcription factor binding models for human and mouse via large-scale ChIP-Seq analysis", Nucleic Acids Res, 46, pp.D252~D259 (2018)
- Weirauch, M. T., "Determination and inference of eukaryotic transcription factor sequence specificity", Cell, 158, pp.1431~1443 (2014)
- Cheneby, J., "ReMap 2018 : An updated atlas of regulatory regions from an integrative analysis of DNAbinding ChIP-seq experiments", Nucleic Acids Res, 46, pp.D267~D275 (2018)
- Luo, S. T., "The promotion of erythropoiesis via the regulation of reactive oxygen species by lactic acid", Sci. Rep, 7, pp.38105~ (2017)
- Trainor, C. D., "GATA-1associates with and inhibits p53", Blood, 114, pp.165~173 (2009)
- Inoue, H., "Target genes of the largest human SWI", SNF complex subunit control cell growth, 2011, pp.434, 83~92
- Weiss, M. J., "Transcription factor GATA-1 permits survival and maturation of erythroid precursors by preventing apoptosis", P. Natl Acad. Sci. USA, 92, pp.9623~9627 (1995)
- Batie, M., "Hypoxia and chromatin : A focus on transcriptional repression mechanisms", Biomedicines, 6, pp.47~ (2018)
- Kelso, T. W. R., "Chromatin accessibility underlies synthetic lethality of SWI", SNF subunits in ARID1A-mutant cancers, 2017, pp.6, e30506~
- Morin, S., "GATA-dependent recruitment of MEF2 proteins to target promoters", EMBO J, 19, pp.2046~2055 (2000)
- Lee, H. Y., "PPAR-alpha and glucocorticoid receptor synergize to promote erythroid progenitor self-renewal", Nature, 522, pp.474~477 (2015)
- Abe, M., "GATA-6 is involved in PPARgamma-mediated activation of differentiated phenotype in human vascular smooth muscle cells", Arterioscler. Thromb. Vas, 23, pp.404~410 (2003)
- Kingsley, P. D., "Ontogeny of erythroid gene expression", Blood, 121, pp.e5~e13 (2013)
- Lin, W. C., "The role of Sp1 and EZH2 in the regulation of LMX1A in cervical cancer cells", Biochim. Biophys. Acta, 1833, pp.3206~3217 (2013)
- Kwon, H., "Nucleosome disruption and enhancement of activator binding by a human Sw1", Snf Complex, 1994, pp.370, 477~481
- OwenHughes, T., "Persistent site-specific remodeling of a nucleosome array by transient action of the SWI", SNF complex, 1996, pp.273, 513~516
- Raab, J. R., "Genome-wide transcriptional regulation mediated by biochemically distinct SWI", SNF complexes, 2015, pp.11, e1005748~
- Cai, W., "Enhancer dependence of cell-type-specific gene expression increases with developmental age", P. Natl. Acad. Sci. USA, 117, pp.21450~21458 (2020)
- Kindrick, J. D., "Hypoxic regulation of gene transcription and chromatin : Cause and effect", Int. J. Mol. Sci, 21, pp.8320~ (2020)
- Melvin, A., "Chromatin as an oxygen sensor and active player in the hypoxia response", Cell. Signal, 24, pp.35~43 (2012)
- Crispino, J. D., "GATA factor mutations in hematologic disease", Blood, 129, pp.2103~2110 (2017)
- Marion, W., "An induced pluripotent stem cell model of Fanconi anemia reveals mechanisms of p53-driven progenitor cell differentiation", Blood Adv, 4, pp.4679~4692 (2020)