Regulation of LMO2 mRNA and protein expression in erythroid differentiation

Low oxygen and temperature pose key physiological challenges for endotherms living on the Qinghai-Tibetan Plateau (QTP). Molecular adaptations to high-altitude living have been detected in the genomes of Tibetans, their domesticated animals and a few wild species, but the contribution of transcriptional variation to altitudinal adaptation remains to be determined. Here we studied a top QTP predator, the saker falcon, and analysed how the transcriptome has become modified to cope with the stresses of hypoxia and hypothermia. Using a hierarchical design to study saker populations inhabiting grassland, steppe/desert and highland across Eurasia, we found that the QTP population is already distinct despite having colonized the Plateau <2000 years ago. Selection signals are limited at the cDNA level, but of only seventeen genes identified, three function in hypoxia and four in immune response. Our results show a significant role for RNA transcription: 50% of upregulated transcription factors were related to hypoxia responses, differentiated modules were significantly enriched for oxygen transport, and importantly, divergent EPAS1 functional variants with a refined co-expression network were identified. Conservative gene expression and relaxed immune gene variation may further reflect adaptation to hypothermia. Our results exemplify synergistic responses between DNA polymorphism and RNA expression diversity in coping with common stresses, underpinning the successful rapid colonization of a top predator onto the QTP. Importantly, molecular mechanisms underpinning Correspondence: Xiangjiang Zhan, Fax: +86 (0)1064807099; E-mail: zhanxj@ioz.ac.cn 1 These two authors contributed equally to the paper. highland adaptation involve relatively few genes, but are nonetheless more complex than previously thought and involve fine-tuned transcriptional responses and genomic adaptation.

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“…EPAS 1 , Hemoglobin , LDB1 ) are associated with hypoxia responses found in previous studies (e.g. Brandt & Koury ; Yi et al . ).…”

Section: Discussionsupporting

confidence: 64%

“…EPAS 1, Hemoglobin, LDB1) are associated with hypoxia responses found in previous studies (e.g. Brandt & Koury 2009;Yi et al 2010). In contrast to the limited selection signals detected from the cDNA sequences, we uncovered a series of expression responses of QH sakers to hypoxia.…”

Section: Low-oxygen Adaptation In Qtp Sakersmentioning

confidence: 55%

Population transcriptomes reveal synergistic responses of DNA polymorphism and RNA expression to extreme environments on the Qinghai–Tibetan Plateau in a predatory bird

Pan

Zhang

Rong³

et al. 2017

Molecular Ecology

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“…48 Transcription factors such as LMO2 were also identified as aberrantly methylated in transformed samples. 49 In conclusion, our results indicate that: 1) the three types of MPNs analyzed in our study show a distinct DNA methylation signature from healthy donors, but the same pattern of aberrant DNA methylation among pathologies, and, therefore, changes in DNA methylation, can not explain the differences in phenotype of these three entities; 2) genes differentially methylated in MPNs could be involved in the pathogenesis of these diseases, for example, by deregulating the NF-κB pathway; 3) MPNs transformed to acute leukemia have an increased number of differentially methylated genes compared to MPNs in chronic phase, and these genes overlap with those seen in primary AML; and 4) differential DNA methylation of IFN pathway genes may play a role in disease progression. Functional studies will be required to clarify the role of DNA methylation in the deregulation of these pathways in MPNs to determine if targeting of these pathways or the use of epigenetic drugs may help prevent disease progression.…”

Section: Discussionmentioning

confidence: 99%

Aberrant DNA methylation profile of chronic and transformed classic Philadelphia-negative myeloproliferative neoplasms

et al. 2013

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“…LMO2 has been shown to be required for the development of normal haematopoiesis. In particular, it influences erythroid differentiation by assembling the basic helix–loop–helix proteins TAL1 and E47, the zinc finger domain containing GATA‐1 and the LIM‐domain interacting protein LDB1 3–9 . It has been demonstrated that homozygous LMO2 −/− mice show failure of yolk sac erythropoiesis and embryonic lethality 10 .…”

Section: Introductionmentioning

confidence: 99%

Detection of LIM domain only 2 (LMO2) in normal human tissues and haematopoietic and non‐haematopoietic tumours using a newly developed rabbit monoclonal antibody

et al. 2012

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2012) HistopathologyDetection of LIM domain only 2 (LMO2) in normal human tissues and haematopoietic and non-haematopoietic tumours using a newly developed rabbit monoclonal antibody Aims: We describe a new rabbit monoclonal antibody, raised against a fixation-resistant epitope of the transcription regulator LIM domain only 2 (LMO2). Methods and results: Lymphoma cell lines and a large series of normal and neoplastic samples were investigated by Western blot and immunohistochemistry. The antibody detected nuclear positivity for the protein, with the exception of a proportion of classical Hodgkin lymphomas (HLs), peripheral T cell lymphomas (PTCLs) and solid tumours that showed granular cytoplasmic staining. In normal lympho-haematopoietic tissues, LMO2 was expressed at different intensities by CD34 + blasts, haematopoietic precursors, germinal centre (GC), mantle and splenic marginal zone B cells. While reactive with only scattered elements in the thymus and nine of 237 PTCLs, the antibody stained 31 of 39 T-acute lymphoblastic lymphoma ⁄ leukaemias (T-ALLs) and the T-ALL-derived human leukaemic cell line, CCRF-CEM. LMO2 was found in 88% of B-acute lymphoblastic lymphoma ⁄ leukaemias (B-ALLs), 5% chronic lymphocytic leukaemias (CLLs) and 14%, 57% and 41% of mantle, follicular and Burkitt lymphomas, respectively. In the setting of diffuse large B cell lymphomas (DLBCLs), LMO2-positivity was related strongly to a GC phenotype. LMO2 was found in 83% primary mediastinal large B cell lymphomas (PMBLs) and 100% nodular lymphocyte predominant Hodgkin lymphomas (NLPHLs), whereas only 10% of classical HLs were stained. Acute and chronic myeloid leukaemias were usually positive. Conclusions: The new anti-LMO2 antibody can be applied confidently to routine sections, contributing to the differential diagnosis of several lymphoma subtypes, subtyping of DLBCLs and potential development of innovative therapies.

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Regulation of LMO2 mRNA and protein expression in erythroid differentiation

Cited by 16 publications

References 16 publications

Population transcriptomes reveal synergistic responses of DNA polymorphism and RNA expression to extreme environments on the Qinghai–Tibetan Plateau in a predatory bird

Population transcriptomes reveal synergistic responses of DNA polymorphism and RNA expression to extreme environments on the Qinghai–Tibetan Plateau in a predatory bird

Aberrant DNA methylation profile of chronic and transformed classic Philadelphia-negative myeloproliferative neoplasms

Detection of LIM domain only 2 (LMO2) in normal human tissues and haematopoietic and non‐haematopoietic tumours using a newly developed rabbit monoclonal antibody

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