Your browser doesn't support javascript.
loading
Chromatin occupancy and epigenetic analysis reveal new insights into the function of the GATA1 N terminus in erythropoiesis.
Ling, Te; Birger, Yehudit; Stankiewicz, Monika J; Ben-Haim, Nissim; Kalisky, Tomer; Rein, Avigail; Kugler, Eitan; Chen, Wei; Fu, Chunling; Zhang, Kevin; Patel, Hiral; Sikora, Jacek W; Goo, Young Ah; Kelleher, Neil; Zou, Lihua; Izraeli, Shai; Crispino, John D.
Afiliación
  • Ling T; Division of Hematology and Oncology, Northwestern University Feinberg School of Medicine, Chicago, IL.
  • Birger Y; The Gene Development and Environment Pediatric Research Institute, Pediatric Hemato-Oncology, Edmond and Lily Safra Children's Hospital, Sheba Medical Center, Tel Hashomer, Ramat Gan, Israel.
  • Stankiewicz MJ; Department of Human Molecular Genetics and Biochemistry, Sackler Medical School, Tel Aviv University, Tel Aviv, Israel.
  • Ben-Haim N; Division of Pediatric Hematology and Oncology, Schneider Children's Medical Center of Israel, Petach Tikva, Israel.
  • Kalisky T; Division of Hematology and Oncology, Northwestern University Feinberg School of Medicine, Chicago, IL.
  • Rein A; Faculty of Engineering and Institute for Nanotechnology and Advanced Materials, Bar-Ilan University, Ramat Gan, Israel.
  • Kugler E; Faculty of Engineering and Institute for Nanotechnology and Advanced Materials, Bar-Ilan University, Ramat Gan, Israel.
  • Chen W; The Gene Development and Environment Pediatric Research Institute, Pediatric Hemato-Oncology, Edmond and Lily Safra Children's Hospital, Sheba Medical Center, Tel Hashomer, Ramat Gan, Israel.
  • Fu C; Department of Human Molecular Genetics and Biochemistry, Sackler Medical School, Tel Aviv University, Tel Aviv, Israel.
  • Zhang K; Division of Pediatric Hematology and Oncology, Schneider Children's Medical Center of Israel, Petach Tikva, Israel.
  • Patel H; The Gene Development and Environment Pediatric Research Institute, Pediatric Hemato-Oncology, Edmond and Lily Safra Children's Hospital, Sheba Medical Center, Tel Hashomer, Ramat Gan, Israel.
  • Sikora JW; Department of Human Molecular Genetics and Biochemistry, Sackler Medical School, Tel Aviv University, Tel Aviv, Israel.
  • Goo YA; Division of Pediatric Hematology and Oncology, Schneider Children's Medical Center of Israel, Petach Tikva, Israel.
  • Kelleher N; Division of Hematology and Oncology, Northwestern University Feinberg School of Medicine, Chicago, IL.
  • Zou L; Blood Disease Institute, Xuzhou Medical University, Xuzhou, China.
  • Izraeli S; Division of Hematology and Oncology, Northwestern University Feinberg School of Medicine, Chicago, IL.
  • Crispino JD; Division of Hematology and Oncology, Northwestern University Feinberg School of Medicine, Chicago, IL.
Blood ; 134(19): 1619-1631, 2019 11 07.
Article en En | MEDLINE | ID: mdl-31409672
Mutations in GATA1, which lead to expression of the GATA1s isoform that lacks the GATA1 N terminus, are seen in patients with Diamond-Blackfan anemia (DBA). In our efforts to better understand the connection between GATA1s and DBA, we comprehensively studied erythropoiesis in Gata1s mice. Defects in yolks sac and fetal liver hematopoiesis included impaired terminal maturation and reduced numbers of erythroid progenitors. RNA-sequencing revealed that both erythroid and megakaryocytic gene expression patterns were altered by the loss of the N terminus, including aberrant upregulation of Gata2 and Runx1. Dysregulation of global H3K27 methylation was found in the erythroid progenitors upon loss of N terminus of GATA1. Chromatin-binding assays revealed that, despite similar occupancy of GATA1 and GATA1s, there was a striking reduction of H3K27me3 at regulatory elements of the Gata2 and Runx1 genes. Consistent with the observation that overexpression of GATA2 has been reported to impair erythropoiesis, we found that haploinsufficiency of Gata2 rescued the erythroid defects of Gata1s fetuses. Together, our integrated genomic analysis of transcriptomic and epigenetic signatures reveals that, Gata1 mice provide novel insights into the role of the N terminus of GATA1 in transcriptional regulation and red blood cell maturation which may potentially be useful for DBA patients.
Asunto(s)
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Eritropoyesis / Factor de Transcripción GATA1 Límite: Animals Idioma: En Revista: Blood Año: 2019 Tipo del documento: Article Pais de publicación: Estados Unidos
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Eritropoyesis / Factor de Transcripción GATA1 Límite: Animals Idioma: En Revista: Blood Año: 2019 Tipo del documento: Article Pais de publicación: Estados Unidos