Unknown,Transcriptomics,Genomics,Proteomics

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Autophagy driven by a master regulator of hematopoiesis

ABSTRACT: Developmental and homeostatic remodeling of cellular organelles is mediated by a complex process termed autophagy. The cohort of proteins that constitute the autophagy machinery function in a multistep biochemical pathway. Though components of the autophagy machinery are broadly expressed, autophagy can occur in specialized cellular contexts, and mechanisms underlying cell type-specific autophagy are poorly understood. We demonstrate that the master regulator of hematopoiesis GATA-1 directly activates transcription of genes encoding the essential autophagy component Microtubule Associated Protein 1 Light Chain 3B (LC3B) and its homologs (MAP1LC3A, GABARAP, GABARAPL1, GATE-16). In addition, GATA-1 directly activates genes involved in the biogenesis/function of lysosomes, which mediate autophagic protein turnover. We demonstrate that GATA-1 utilizes the forkhead protein FoxO3 to activate select autophagy genes. GATA-1-dependent LC3B induction is tightly coupled to accumulation of the active form of LC3B and autophagosomes, which mediate mitochondrial clearance as a critical step in erythropoiesis. These results illustrate a novel mechanism by which a master regulator of development establishes a genetic network to instigate cell type-specific autophagy. Genome-wide maps of GATA1 factor occupancy in primary human PBMC derived erythroblasts

ORGANISM(S): Homo sapiens

SUBMITTER: Emery Bresnick

PROVIDER: E-GEOD-32491 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Autophagy driven by a master regulator of hematopoiesis.

Kang Yoon-A YA Sanalkumar Rajendran R O'Geen Henriette H Linnemann Amelia K AK Chang Chan-Jung CJ Bouhassira Eric E EE Farnham Peggy J PJ Keles Sunduz S Bresnick Emery H EH

Molecular and cellular biology 20111024 1

Developmental and homeostatic remodeling of cellular organelles is mediated by a complex process termed autophagy. The cohort of proteins that constitute the autophagy machinery functions in a multistep biochemical pathway. Though components of the autophagy machinery are broadly expressed, autophagy can occur in specialized cellular contexts, and mechanisms underlying cell-type-specific autophagy are poorly understood. We demonstrate that the master regulator of hematopoiesis, GATA-1, directly ...[more]

PMID: 22025678

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Autophagy driven by a master regulator of hematopoiesis

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Autophagy driven by a master regulator of hematopoiesis.

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