Chromatin Architecture and Transcription Factor Binding Regulate Expression of Erythrocyte Membrane Protein Genes
- 1 October 2009
- journal article
- research article
- Published by Informa UK Limited in Molecular and Cellular Biology
- Vol. 29 (20), 5399-5412
- https://doi.org/10.1128/mcb.00777-09
Abstract
Erythrocyte membrane protein genes serve as excellent models of complex gene locus structure and function, but their study has been complicated by both their large size and their complexity. To begin to understand the intricate interplay of transcription, dynamic chromatin architecture, transcription factor binding, and genomic organization in regulation of erythrocyte membrane protein genes, we performed chromatin immunoprecipitation (ChIP) coupled with microarray analysis and ChIP coupled with massively parallel DNA sequencing in both erythroid and nonerythroid cells. Unexpectedly, most regions of GATA-1 and NF-E2 binding were remote from gene promoters and transcriptional start sites, located primarily in introns. Cooccupancy with FOG-1, SCL, and MTA-2 was found at all regions of GATA-1 binding, with cooccupancy of SCL and MTA-2 also found at regions of NF-E2 binding. Cooccupancy of GATA-1 and NF-E2 was found frequently. A common signature of histone H3 trimethylation at lysine 4, GATA-1, NF-E2, FOG-1, SCL, and MTA-2 binding and consensus GATA-1-E-box binding motifs located 34 to 90 bp away from NF-E2 binding motifs was found frequently in erythroid cell-expressed genes. These results provide insights into our understanding of membrane protein gene regulation in erythropoiesis and the regulation of complex genetic loci in erythroid and nonerythroid cells and identify numerous candidate regions for mutations associated with membrane-linked hemolytic anemia.Keywords
This publication has 125 references indexed in Scilit:
- Complex developmental patterns of histone modifications associated with the human β-globin switch in primary cellsExperimental Hematology, 2009
- Locus control region mediated regulation of adult β‐globin gene expressionJournal of Cellular Biochemistry, 2008
- Chromatin loops in gene regulationBiochimica et Biophysica Acta (BBA) - Gene Regulatory Mechanisms, 2008
- Exchange of GATA Factors Mediates Transitions in Looped Chromatin Organization at a Developmentally Regulated Gene LocusMolecular Cell, 2008
- RNA polymerase is poised for activation across the genomeNature Genetics, 2007
- Activator-Mediated Recruitment of the MLL2 Methyltransferase Complex to the β-Globin LocusMolecular Cell, 2007
- Long-range chromosomal interactions regulate the timing of the transition between poised and active gene expressionThe EMBO Journal, 2007
- Analysis of the Vertebrate Insulator Protein CTCF-Binding Sites in the Human GenomeCell, 2007
- Expression of GATA-1 in a Non-hematopoietic Cell Line Induces β-Globin Locus Control Region Chromatin Structure Remodeling and an Erythroid Pattern of Gene ExpressionJournal of Molecular Biology, 2007
- Differential sensitivities of transcription factor target genes underlie cell type-specific gene expression profilesProceedings of the National Academy of Sciences of the United States of America, 2006