MTA2/NuRD Regulates B Cell Development and Cooperates with OCA-B in Controlling the Pre-B to Immature B Cell Transition

Lu, Xiangdong; Chu, Chi-Shuen; Fang, Terry; Rayon-Estrada, Violeta; Fang, Fang; Patke, Alina; Qian, Yuping; Clarke, Stephen H.; Melnick, Ari; Zhang, Yi; Papavasiliou, F. Nina; Roeder, Robert G.

doi:10.1016/j.celrep.2019.06.029

Cited by 35 publications

(26 citation statements)

References 53 publications

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“…IGLL1 is part of the immunoglobulin gene superfamily, and its expression is closely related to humoral immunity 22 . It is associated with immune cell progression 23 . IGLL1 is thought to be a component of pre-BCR (precursor B cell antigen receptor) 24 .…”

Section: Discussionmentioning

confidence: 99%

Tumor mutation burden (TMB)-associated signature constructed to predict survival of lung squamous cell carcinoma patients

Duan

Chen

2021

Sci Rep

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Lung squamous cell carcinoma (LUSC) is a common type of lung cancer with high incidence and mortality rate. Tumor mutational burden (TMB) is an emerging biomarker for selecting patients with non-small cell lung cancer (NSCLC) for immunotherapy. This study aimed to reveal TMB involved in the mechanisms of LUSC and develop a model to predict the overall survival of LUSC patients. The information of patients with LUSC were obtained from the cancer genome atlas database (TCGA). Differentially expressed genes (DEGs) between low- and the high-TMB groups were identified and taken as nodes for the protein–protein interaction (PPI) network construction. Gene oncology (GO) enrichment analysis and gene set enrichment analysis (GSEA) were used to investigate the potential molecular mechanism. Then, we identified the factors affecting the prognosis of LUSC through cox analysis, and developed a risk score signature. Kaplan–Meier method was conducted to analyze the difference in survival between the high- and low-risk groups. We constructed a nomogram based on the risk score model and clinical characteristics to predict the overall survival of patients with LUSC. Finally, the signature and nomogram were further validated by using the gene expression data downloaded from the Gene Expression Omnibus (GEO) database. 30 DEGs between high- and low-TMB groups were identified. PPI analysis identified CD22, TLR10, PIGR and SELE as the hub genes. Cox analysis indicated that FAM107A, IGLL1, SELE and T stage were independent prognostic factors of LUSC. Low-risk scores group lived longer than that of patients with high-risk scores in LUSC. Finally, we built a nomogram that integrated the clinical characteristics (TMN stage, age, gender) with the three-gene signature to predict the survival probability of LUSC patients. Further verification in the GEO dataset. TMB might contribute to the pathogenesis of LUSC. TMB-associated genes can be used to develope a model to predict the OS of lung squamous cell carcinoma patients.

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Section: Discussionmentioning

confidence: 99%

Tumor mutation burden (TMB)-associated signature constructed to predict survival of lung squamous cell carcinoma patients

Duan

Chen

2021

Sci Rep

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“…MTA2 also cooperates with OCA-B to regulate the pre-B cell to immature B cell transition via repressing the Igll1 and VpreB1 genes. 67 …”

Section: Chromatin Remodeling Complexes (Crcs)mentioning

confidence: 99%

Interplay between cofactors and transcription factors in hematopoiesis and hematological malignancies

Wang

et al. 2021

Sig Transduct Target Ther

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Hematopoiesis requires finely tuned regulation of gene expression at each stage of development. The regulation of gene transcription involves not only individual transcription factors (TFs) but also transcription complexes (TCs) composed of transcription factor(s) and multisubunit cofactors. In their normal compositions, TCs orchestrate lineage-specific patterns of gene expression and ensure the production of the correct proportions of individual cell lineages during hematopoiesis. The integration of posttranslational and conformational modifications in the chromatin landscape, nucleosomes, histones and interacting components via the cofactor–TF interplay is critical to optimal TF activity. Mutations or translocations of cofactor genes are expected to alter cofactor–TF interactions, which may be causative for the pathogenesis of various hematologic disorders. Blocking TF oncogenic activity in hematologic disorders through targeting cofactors in aberrant complexes has been an exciting therapeutic strategy. In this review, we summarize the current knowledge regarding the models and functions of cofactor–TF interplay in physiological hematopoiesis and highlight their implications in the etiology of hematological malignancies. This review presents a deep insight into the physiological and pathological implications of transcription machinery in the blood system.

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“…Similar to the Pax5 knockout (Nutt et al, 1999), loss of IKAROS DNA-binding activity prevents lymphoid differentiation (Zhang et al, 2011). NuRD co-operates directly with IKAROS to repress HSC self-renewal and subsequent myeloid differentiation, permitting early lymphoid development (O'Neill et al, 2000;Williams et al, 2004;Yoshida et al, 2008;Zhang et al, 2011;Hosokawa et al, 2013;Lu et al, 2019). We found that the abrogation of this pathway…”

Section: Discussionmentioning

confidence: 66%

“…Similar to the Pax5 knockout (40), loss of IKAROS DNA-binding activity prevents lymphoid differentiation (29). NuRD co-operates directly with IKAROS to repress HSC self-renewal and subsequent myeloid differentiation, permitting early lymphoid development (29,44,45).…”

Section: Discussionmentioning

confidence: 98%

Epigenetic regulator genes direct lineage switching in MLL-AF4 leukaemia

Tirtakusuma

Szołtysek

Milne

et al. 2021

Preprint

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The fusion gene MLL-AF4 defines a high-risk subtype of pro-B acute lymphoblastic leukaemia. However, relapse can be associated with a switch from acute lymphoblastic to acute myeloid leukaemia. Here we show that these myeloid relapses share oncogene fusion breakpoints with their matched lymphoid presentations and can originate in either early, multipotent progenitors or committed B-cell precursors. Lineage switching is linked to substantial changes in chromatin accessibility and rewiring of transcriptional programmes indicating that the execution and maintenance of lymphoid lineage differentiation is impaired. We show that this subversion is recurrently associated with the dysregulation of repressive chromatin modifiers, notably the nucleosome remodelling and deacetylation complex, NuRD. In addition to mutations, we show differential expression or alternative splicing of NuRD members and other genes is able to reprogram the B lymphoid into a myeloid gene regulatory network. Lineage switching in MLL-AF4 leukaemia is therefore driven and maintained by defunct epigenetic regulation.

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MTA2/NuRD Regulates B Cell Development and Cooperates with OCA-B in Controlling the Pre-B to Immature B Cell Transition

Cited by 35 publications

References 53 publications

Tumor mutation burden (TMB)-associated signature constructed to predict survival of lung squamous cell carcinoma patients

Tumor mutation burden (TMB)-associated signature constructed to predict survival of lung squamous cell carcinoma patients

Interplay between cofactors and transcription factors in hematopoiesis and hematological malignancies

Epigenetic regulator genes direct lineage switching in MLL-AF4 leukaemia

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