Defining the NSD2 interactome: PARP1 PARylation reduces NSD2 histone methyltransferase activity and impedes chromatin binding Genomics and Proteomics

In this study, we utilized proximity-based labeling (BioID) combined with label-free quantitative MS to identify high confidence NSD2 interacting partners in MM cells. The top 24 proteins identified were involved in maintaining chromatin structure, transcriptional regulation, RNA pre-spliceosome assembly, and DNA damage. Among these, an important DNA damage regulator, poly(ADP-ribose) polymerase 1 (PARP1), was discovered. PARP1 and NSD2 have been found to be recruited to DNA double strand breaks upon damage and H3K36me2 marks are enriched at damage sites. We demonstrate that PARP1 regulates NSD2 via PARylation upon oxidative stress. In vitro assays suggest the PARylation significantly reduces NSD2 histone methyltransferase activity. Furthermore, PARylation of NSD2 inhibits its ability to bind to nucleosomes and further get recruited at NSD2-regulated genes, suggesting PARP1 regulates NSD2 localization and H3K36me2 balance. This work provides clear evidence of cross-talk between PARylation and histone methylation and offers new directions to characterize NSD2 function in DNA damage response, transcriptional regulation, and other pathways.
Source: Journal of Biological Chemistry - Category: Chemistry Authors: Tags: Genomics and Proteomics Source Type: research

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Publication date: Available online 27 August 2019Source: Clinical Lymphoma Myeloma and LeukemiaAuthor(s): Weerapat Owattanapanich, Pongprueth Rujirachun, Patompong Ungprasert, Jassada Buaboonnam, Piti TechavichitAbstractBackgroundThe presence of Philadelphia (Ph)-like ALL among patients with acute lymphoblastic leukemia (ALL) may indicate a poor prognosis similar to Philadelphia positive (Ph+) ALL although the data are still inconclusive and the prevalence of Ph-like ALL varied considerably across the studies.MethodsThe current systematic review and meta-analysis were conducted with the aims to identify all cohort studies ...
Source: Clinical Lymphoma Myeloma and Leukemia - Category: Cancer & Oncology Source Type: research
Publication date: Available online 26 August 2019Source: Clinical Lymphoma Myeloma and LeukemiaAuthor(s): Hyunkyung Park, Ja Min Byun, Youngil Koh, Sung-Soo Yoon, Hyejoo Park, Jayoun Lee, Sang-Jin Shin, Jeonghwan YoukAbstractBackground/AimThe optimal the conditioning regimens for allogeneic hematopoietic stem cell transplantation (HSCT), especially for East Asian patients, remains unknown.Patients and MethodsWe collected and analyzed clinical and survival data of 4,255 patients from the Korean National Health Insurance Claims Database.ResultsBetween 1,562 myeloablative conditioning (MAC) and 2,693 non-myeloablative conditi...
Source: Clinical Lymphoma Myeloma and Leukemia - Category: Cancer & Oncology Source Type: research
The presence of Philadelphia (Ph)-like ALL among patients with acute lymphoblastic leukemia (ALL) may indicate a poor prognosis similar to Philadelphia positive (Ph+) ALL although the data are still inconclusive and the prevalence of Ph-like ALL varied considerably across the studies.
Source: Clinical Lymphoma, Myeloma and Leukemia - Category: Hematology Authors: Tags: Original Study Source Type: research
Auer rods were first described in the cytoplasm of leukemia blasts by John Auer in 1906. Auer rods are commonly seen in myeloid progenitors, and serve as a diagnostic morphological feature of acute myeloid leukemia (AML) [1]. The differential diagnosis of hematopoietic neoplasms relies on the detection of cytoplasmic inclusions resembling Auer rods. Auer rod-like inclusions have been described in multiple myeloma [2], prolymphocytic leukemia (PLL) [3], B-cell acute lymphoblastic leukemia [4], chronic lymphocytic leukemia [4], splenic lymphoma [5] and nodal marginal zone lymphoma [6], which are quite distinct from the needl...
Source: Experimental Hematology - Category: Hematology Authors: Tags: Brief Communication Source Type: research
ConclusionThe use of a pediatric-inspired protocol for high-risk AYA ALL patients was effective and well tolerated with improvement in OS and DFS compared with historical data using adult protocols in such populations.
Source: Clinical Lymphoma Myeloma and Leukemia - Category: Cancer & Oncology Source Type: research
Publication date: August 2019Source: Clinical Lymphoma Myeloma and Leukemia, Volume 19, Issue 8Author(s): Shilpa Paul, Caitlin R. Rausch, Mary Alma Welch, Hagop M. Kantarjian, Elias J. JabbourAbstractThe treatment of adult acute lymphoblastic leukemia (ALL) has largely followed the successful pediatric model that uses multi-agent chemotherapy regimens. Although cytotoxic chemotherapy can induce complete remissions, elderly patients are frequently unable to tolerate its intensity owing to toxicities and comorbidities. Elderly patients particularly often relapse, leading to a 5-year overall survival (OS) of only 20%. In an e...
Source: Clinical Lymphoma Myeloma and Leukemia - Category: Cancer & Oncology Source Type: research
Contributors : Cates Mallaney ; Elizabeth L Ostrander ; Hamza Celik ; Ashley C Kramer ; Andrew Martens ; Alok Kothari ; Won K Koh ; Emily Haussler ; Grant A ChallenSeries Type : Expression profiling by high throughput sequencing ; Genome binding/occupancy profiling by high throughput sequencingOrganism : Mus musculusRecent studies have indicated that the histone 3 lysine 27 (H3K27me2/3) demethylase KDM6B (JMJD3) is frequently upregulated in a myriad of blood disorders including myelodysplastic syndrome (MDS), T-cell acute lymphoblastic leukemia (T-ALL), and multiple myeloma (MM) suggesting it may have important functions i...
Source: GEO: Gene Expression Omnibus - Category: Genetics & Stem Cells Tags: Expression profiling by high throughput sequencing Genome binding/occupancy profiling by high throughput sequencing Mus musculus Source Type: research
Chimeric antigen receptor (CAR)-modified T cell therapy is a rapidly emerging immunotherapeutic approach that is revolutionizing cancer treatment. The impressive clinical results obtained with CAR-T cell therapy in patients with acute lymphoblastic leukemia and lymphoma have fueled the development of CAR-T cells targeting other malignancies, including multiple myeloma (MM). The field of CAR-T cell therapy for MM is still in its infancy, but remains promising. To date, most studies have been performed with B cell maturation antigen (BCMA)-targeted CARs, for which high response rates have been obtained in early-phase clinica...
Source: Frontiers in Immunology - Category: Allergy & Immunology Source Type: research
Publication date: Available online 3 July 2019Source: Clinical Lymphoma Myeloma and LeukemiaAuthor(s): Shilpa Paul, Caitlin R. Rausch, Mary Alma Welch, Hagop M. Kantarjian, Elias J. JabbourAbstractThe treatment of adult acute lymphoblastic leukemia (ALL) has largely followed the successful pediatric model that uses multiagent chemotherapy regimens. Although cytotoxic chemotherapy can induce complete remissions, elderly patients are frequently unable to tolerate its intensity due to toxicities and comorbidities. Elderly patients particularly often relapse, leading to a 5-year overall survival (OS) of only 20%. In an effort ...
Source: Clinical Lymphoma Myeloma and Leukemia - Category: Cancer & Oncology Source Type: research
Abstract The treatment of adult acute lymphoblastic leukemia (ALL) has largely followed the successful pediatric model that uses multi-agent chemotherapy regimens. Although cytotoxic chemotherapy can induce complete remissions, elderly patients are frequently unable to tolerate its intensity owing to toxicities and comorbidities. Elderly patients particularly often relapse, leading to a 5-year overall survival (OS) of only 20%. In an effort to improve outcomes while minimizing toxicities, novel targeted therapies have been developed: monoclonal antibodies against CD19, CD20, and CD22; tyrosine kinase inhibitors; c...
Source: Clinical Lymphoma and Myeloma - Category: Cancer & Oncology Authors: Tags: Clin Lymphoma Myeloma Leuk Source Type: research
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