BCL2L1 is associated with γ-globin gene expression

Dai, Yan; Shaikho, Elmutaz M.; Perez, Jessica G.; Wilson, Carolyn A.; Liu, Lesley Y.; White, Mitchell R.; Farrell, John; Chui, David H.K.; Sebastiani, Paola; Steinberg, Martin H.

doi:10.1182/bloodadvances.2019032243

Cited by 10 publications

(5 citation statements)

References 25 publications

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“…Significant progress has been made toward uncovering the functionally relevant variants in these loci, such as rs7482144 in HBG2, rs1427407 in BCL11A, and rs66650371 in HBS1L-MYB. Two other loci have been found to alter HbF level: FRMPD4 (Xp22.2) among Tanzanian SCD patients (125) and BCL2L1 (20q11.21), which is yet to be seen in Africa (27). Nevertheless, many of the studies on polymorphisms in HbF quantitative trait loci have involved non-African populations or African Americans (38), Black British people of West African origin, and Afro-Caribbeans or Afro-Brazilians (24).…”

Section: Common and Rare Monogenic Diseases: Genetic And Locus Hetero...mentioning

confidence: 99%

Five Priorities of African Genomics Research: The Next Frontier

Wonkam

Munung

Dandara

et al. 2022

Annu. Rev. Genom. Hum. Genet.

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To embrace the prospects of accurately diagnosing thousands of monogenic conditions, predicting disease risks for complex traits or diseases, tailoring treatment to individuals’ pharmacogenetic profiles, and potentially curing some diseases, research into African genomic variation is a scientific imperative. African genomes harbor millions of uncaptured variants accumulated over 300,000 years of modern humans’ evolutionary history, with successive waves of admixture, migration, and natural selection combining with extensive ecological diversity to create a broad and exceptional genomic complexity. Harnessing African genomic complexity, therefore, will require sustained commitment and equitable collaboration from the scientific community and funding agencies. African governments must support academic public research and industrial partnerships that build the necessary genetic medicine workforce, utilize the emerging genomic big data to develop expertise in computer science and bioinformatics, and evolve national and global governance frameworks that recognize the ethical implications of data-driven genomic research and empower its application in African social, cultural, economic, and religious contexts. Expected final online publication date for the Annual Review of Genomics and Human Genetics, Volume 23 is October 2022. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.

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Section: Common and Rare Monogenic Diseases: Genetic And Locus Hetero...mentioning

confidence: 99%

Five Priorities of African Genomics Research: The Next Frontier

Wonkam

Munung

Dandara

et al. 2022

Annu. Rev. Genom. Hum. Genet.

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“…To this end, hCD34+, HUDEP-1, and HUDEP-2 cells were expanded, differentiated, characterized, and analyzed for small RNA expression at early and late stages of erythroid commitment. Whereas hCD34+ cells are relevant as the hematopoietic stem and progenitor cell population used for therapeutic transplantation, the HUDEP cell lines are now used by many hematological research groups and currently represent an invaluable model for the study of erythropoiesis and therapy development [ 33 , 34 , 35 , 36 , 37 , 38 ]. Since their establishment by Kurita et al based on lentiviral transduction of the doxycycline-inducible human papillomavirus 16 (HPV16)-E6/E7 expression system, HUDEP cells have overwhelmingly replaced other cell lines, such as K562, MEL, and UT-7/EPO, in the analysis of erythropoiesis, owing to their superior similarity to human primary cells.…”

Section: Introductionmentioning

confidence: 99%

Distinct miRNA Signatures and Networks Discern Fetal from Adult Erythroid Differentiation and Primary from Immortalized Erythroid Cells

Papasavva

Papaioannou

Patsali

et al. 2021

IJMS

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MicroRNAs (miRNAs) are small non-coding RNAs crucial for post-transcriptional and translational regulation of cellular and developmental pathways. The study of miRNAs in erythropoiesis elucidates underlying regulatory mechanisms and facilitates related diagnostic and therapy development. Here, we used DNA Nanoball (DNB) small RNA sequencing to comprehensively characterize miRNAs in human erythroid cell cultures. Based on primary human peripheral-blood-derived CD34+ (hCD34+) cells and two influential erythroid cell lines with adult and fetal hemoglobin expression patterns, HUDEP-2 and HUDEP-1, respectively, our study links differential miRNA expression to erythroid differentiation, cell type, and hemoglobin expression profile. Sequencing results validated by reverse-transcription quantitative PCR (RT-qPCR) of selected miRNAs indicate shared differentiation signatures in primary and immortalized cells, characterized by reduced overall miRNA expression and reciprocal expression increases for individual lineage-specific miRNAs in late-stage erythropoiesis. Despite the high similarity of same-stage hCD34+ and HUDEP-2 cells, differential expression of several miRNAs highlighted informative discrepancies between both cell types. Moreover, a comparison between HUDEP-2 and HUDEP-1 cells displayed changes in miRNAs, transcription factors (TFs), target genes, and pathways associated with globin switching. In resulting TF-miRNA co-regulatory networks, major therapeutically relevant regulators of globin expression were targeted by many co-expressed miRNAs, outlining intricate combinatorial miRNA regulation of globin expression in erythroid cells.

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“…After topological structure analysis of protein interaction of all overlapping dual-regulated genes, the top 4 pivotal genes turned out to be HSPA4, GRB2, PRKCA, and BCL2L1. The BCL2L1 encoded protein belongs to the BCL-2 protein family and acts as an anti- or pro-apoptotic regulator involved in a variety of cellular activities ( Dai et al, 2019 ). It is located in the outer mitochondrial membrane and has been shown to regulate the opening of the outer mitochondrial membrane channel (VDAC) which plays an important role in apoptosis.…”

Section: Discussionmentioning

confidence: 99%

Epigenetic Biomarkers Screening of Non-Coding RNA and DNA Methylation Based on Peripheral Blood Monocytes in Smokers

Huang

Zhang

et al. 2022

Front. Genet.

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This study aims to use bioinformatics methods to determine the epigenetic changes in microRNA expression and DNA methylation caused by cigarette smoking. The data of mRNA, miRNA expression, and methylation microarray were obtained from the GEO database to filter differentially expressed genes (DEGs), differentially expressed miRNAs (DEMs), and methylated CpG probes (DMPs) through the limma package. The R clusterProfile package was used for functional annotation and enrichment analysis. The protein-protein interaction (PPI) network was constructed by the String database and visualized in Cytoscape software. Starbase database was employed to predict lncRNA and CirRNA based on the sequence of miRNA, and to establish a regulatory network of ceRNA. By overlapping DEG and DEM, 107 down-miRNA-targeted up-regulated genes and 65 up-miRNA-target down-regulated genes were obtained, which were mainly enriched in autophagy signaling pathways and protein ubiquitination pathways, respectively. In addition, 324 genes with low methylation and high expression and 204 genes with high methylation and low expression were respectively related to the degeneration of the nervous system and the function of the cardiovascular system. Interestingly, 43 genes were up-regulated under the dual regulation of reduced miRNA and hypomethylation, while 14 genes were down-regulated under the dual regulation of increased miRNA and hypermethylation. Ten chemicals have been identified as putative therapeutic agents for pathological conditions caused by smoking. In addition, among these genes, HSPA4, GRB2, PRKCA, and BCL2L1 could play a fundamental role in related diseases caused by smoking and may be used as the biomarkers for precise diagnosis and targets for future therapies of smoking-related diseases.

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BCL2L1 is associated with γ-globin gene expression

Abstract: Key Points BCL2L1 is associated with HbF gene activation.

Cited by 10 publications

References 25 publications

Five Priorities of African Genomics Research: The Next Frontier

Five Priorities of African Genomics Research: The Next Frontier

Distinct miRNA Signatures and Networks Discern Fetal from Adult Erythroid Differentiation and Primary from Immortalized Erythroid Cells

Epigenetic Biomarkers Screening of Non-Coding RNA and DNA Methylation Based on Peripheral Blood Monocytes in Smokers

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