Document Detail


Novel roles for KLF1 in erythropoiesis revealed by mRNA-seq.
MedLine Citation:
PMID:  22835905     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
KLF1 (formerly known as EKLF) regulates the development of erythroid cells from bi-potent progenitor cells via the transcriptional activation of a diverse set of genes. Mice lacking Klf1 die in utero prior to E15 from severe anemia due to the inadequate expression of genes controlling hemoglobin production, cell membrane and cytoskeletal integrity, and the cell cycle. We have recently described the full repertoire of KLF1 binding sites in vivo by performing KLF1 ChIP-seq in primary erythroid tissue (E14.5 fetal liver). Here we describe the KLF1-dependent erythroid transcriptome by comparing mRNA-seq from Klf1(+/+) and Klf1(-/-) erythroid tissue. This has revealed novel target genes not previously obtainable by traditional microarray technology, and provided novel insights into the function of KLF1 as a transcriptional activator. We define a cis-regulatory module bound by KLF1, GATA1, TAL1, and EP300 that coordinates a core set of erythroid genes. We also describe a novel set of erythroid-specific promoters that drive high-level expression of otherwise ubiquitously expressed genes in erythroid cells. Our study has identified two novel lncRNAs that are dynamically expressed during erythroid differentiation, and discovered a role for KLF1 in directing apoptotic gene expression to drive the terminal stages of erythroid maturation.
Authors:
Michael R Tallack; Graham W Magor; Benjamin Dartigues; Lei Sun; Stephen Huang; Jessica M Fittock; Sally V Fry; Evgeny A Glazov; Timothy L Bailey; Andrew C Perkins
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2012-07-26
Journal Detail:
Title:  Genome research     Volume:  22     ISSN:  1549-5469     ISO Abbreviation:  Genome Res.     Publication Date:  2012 Dec 
Date Detail:
Created Date:  2012-12-03     Completed Date:  2013-05-10     Revised Date:  2013-07-12    
Medline Journal Info:
Nlm Unique ID:  9518021     Medline TA:  Genome Res     Country:  United States    
Other Details:
Languages:  eng     Pagination:  2385-98     Citation Subset:  IM    
Affiliation:
Mater Medical Research Institute, Mater Hospital, Brisbane, Queensland 4101, Australia.
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MeSH Terms
Descriptor/Qualifier:
Animals
Apoptosis
Basic Helix-Loop-Helix Transcription Factors / genetics,  metabolism
Blotting, Western
Cell Differentiation
Chromosome Mapping
E1A-Associated p300 Protein / genetics,  metabolism
Erythroid Cells / cytology,  metabolism
Erythropoiesis / genetics*
GATA1 Transcription Factor / genetics,  metabolism
Gene Expression Profiling
Gene Expression Regulation, Developmental*
In Situ Nick-End Labeling
Kruppel-Like Transcription Factors / genetics*,  metabolism
Liver / metabolism
Mice
Mice, Inbred BALB C
Promoter Regions, Genetic
Proto-Oncogene Proteins / genetics,  metabolism
RNA, Messenger / genetics*,  metabolism
Sequence Analysis, RNA / methods
Transcriptome*
Chemical
Reg. No./Substance:
0/Basic Helix-Loop-Helix Transcription Factors; 0/Ep300 protein, mouse; 0/GATA1 Transcription Factor; 0/Gata1 protein, mouse; 0/Kruppel-Like Transcription Factors; 0/Proto-Oncogene Proteins; 0/RNA, Messenger; 0/Tal1 protein, mouse; 0/erythroid Kruppel-like factor; EC 2.3.1.48/E1A-Associated p300 Protein
Comments/Corrections

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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