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Primary sequence and epigenetic determinants of in vivo occupancy of genomic DNA by GATA1
DNA sequence motifs and epigenetic modifications contribute to specific binding by a transcription factor, but the extent to which each feature determines occupancy in vivo is poorly understood. We addressed this question in erythroid cells by identifying DNA segments occupied by GATA1 and measuring...
Autores principales: | , , , , , , , |
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Formato: | Texto |
Lenguaje: | English |
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Oxford University Press
2009
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2790884/ https://www.ncbi.nlm.nih.gov/pubmed/19767611 http://dx.doi.org/10.1093/nar/gkp747 |
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author | Zhang, Ying Wu, Weisheng Cheng, Yong King, David C. Harris, Robert S. Taylor, James Chiaromonte, Francesca Hardison, Ross C. |
author_facet | Zhang, Ying Wu, Weisheng Cheng, Yong King, David C. Harris, Robert S. Taylor, James Chiaromonte, Francesca Hardison, Ross C. |
author_sort | Zhang, Ying |
collection | PubMed |
description | DNA sequence motifs and epigenetic modifications contribute to specific binding by a transcription factor, but the extent to which each feature determines occupancy in vivo is poorly understood. We addressed this question in erythroid cells by identifying DNA segments occupied by GATA1 and measuring the level of trimethylation of histone H3 lysine 27 (H3K27me3) and monomethylation of H3 lysine 4 (H3K4me1) along a 66 Mb region of mouse chromosome 7. While 91% of the GATA1-occupied segments contain the consensus binding-site motif WGATAR, only ∼0.7% of DNA segments with such a motif are occupied. Using a discriminative motif enumeration method, we identified additional motifs predictive of occupancy given the presence of WGATAR. The specific motif variant AGATAA and occurrence of multiple WGATAR motifs are both strong discriminators. Combining motifs to pair a WGATAR motif with a binding site motif for GATA1, EKLF or SP1 improves discriminative power. Epigenetic modifications are also strong determinants, with the factor-bound segments highly enriched for H3K4me1 and depleted of H3K27me3. Combining primary sequence and epigenetic determinants captures 52% of the GATA1-occupied DNA segments and substantially increases the specificity, to one out of seven segments with the required motif combination and epigenetic signals being bound. |
format | Text |
id | pubmed-2790884 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2009 |
publisher | Oxford University Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-27908842009-12-09 Primary sequence and epigenetic determinants of in vivo occupancy of genomic DNA by GATA1 Zhang, Ying Wu, Weisheng Cheng, Yong King, David C. Harris, Robert S. Taylor, James Chiaromonte, Francesca Hardison, Ross C. Nucleic Acids Res Gene Regulation, Chromatin and Epigenetics DNA sequence motifs and epigenetic modifications contribute to specific binding by a transcription factor, but the extent to which each feature determines occupancy in vivo is poorly understood. We addressed this question in erythroid cells by identifying DNA segments occupied by GATA1 and measuring the level of trimethylation of histone H3 lysine 27 (H3K27me3) and monomethylation of H3 lysine 4 (H3K4me1) along a 66 Mb region of mouse chromosome 7. While 91% of the GATA1-occupied segments contain the consensus binding-site motif WGATAR, only ∼0.7% of DNA segments with such a motif are occupied. Using a discriminative motif enumeration method, we identified additional motifs predictive of occupancy given the presence of WGATAR. The specific motif variant AGATAA and occurrence of multiple WGATAR motifs are both strong discriminators. Combining motifs to pair a WGATAR motif with a binding site motif for GATA1, EKLF or SP1 improves discriminative power. Epigenetic modifications are also strong determinants, with the factor-bound segments highly enriched for H3K4me1 and depleted of H3K27me3. Combining primary sequence and epigenetic determinants captures 52% of the GATA1-occupied DNA segments and substantially increases the specificity, to one out of seven segments with the required motif combination and epigenetic signals being bound. Oxford University Press 2009-11 2009-09-18 /pmc/articles/PMC2790884/ /pubmed/19767611 http://dx.doi.org/10.1093/nar/gkp747 Text en © The Author(s) 2009. Published by Oxford University Press. http://creativecommons.org/licenses/by-nc/2.5/uk/ This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/2.5/uk/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Gene Regulation, Chromatin and Epigenetics Zhang, Ying Wu, Weisheng Cheng, Yong King, David C. Harris, Robert S. Taylor, James Chiaromonte, Francesca Hardison, Ross C. Primary sequence and epigenetic determinants of in vivo occupancy of genomic DNA by GATA1 |
title | Primary sequence and epigenetic determinants of in vivo occupancy of genomic DNA by GATA1 |
title_full | Primary sequence and epigenetic determinants of in vivo occupancy of genomic DNA by GATA1 |
title_fullStr | Primary sequence and epigenetic determinants of in vivo occupancy of genomic DNA by GATA1 |
title_full_unstemmed | Primary sequence and epigenetic determinants of in vivo occupancy of genomic DNA by GATA1 |
title_short | Primary sequence and epigenetic determinants of in vivo occupancy of genomic DNA by GATA1 |
title_sort | primary sequence and epigenetic determinants of in vivo occupancy of genomic dna by gata1 |
topic | Gene Regulation, Chromatin and Epigenetics |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2790884/ https://www.ncbi.nlm.nih.gov/pubmed/19767611 http://dx.doi.org/10.1093/nar/gkp747 |
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