The role of chromatin accessibility in directing the widespread, overlapping patterns of Drosophila transcription factor binding

被引:150
作者
Li, Xiao-Yong [2 ,3 ]
Thomas, Sean [1 ]
Sabo, Peter J. [1 ]
Eisen, Michael B. [2 ,3 ,4 ]
Stamatoyannopoulos, John A. [1 ]
Biggin, Mark D. [2 ]
机构
[1] Univ Washington, Dept Genome Sci, Seattle, WA 98195 USA
[2] Univ Calif Berkeley, Lawrence Berkeley Lab, Genom Div, Berkeley, CA 94720 USA
[3] Univ Calif Berkeley, Howard Hughes Med Inst, Berkeley, CA 94720 USA
[4] Univ Calif Berkeley, Dept Mol & Cell Biol, Berkeley, CA 94720 USA
基金
美国国家卫生研究院;
关键词
EMBRYONIC STEM-CELLS; HOMEOPROTEIN-DNA-BINDING; CIS-REGULATORY MODULES; INTERACTIONS IN-VIVO; HEAT-SHOCK GENES; HUMAN GENOME; GLUCOCORTICOID-RECEPTOR; HYPERSENSITIVE SITES; REPRESSOR GRADIENTS; PROTEIN-BINDING;
D O I
10.1186/gb-2011-12-4-r34
中图分类号
Q81 [生物工程学(生物技术)]; Q93 [微生物学];
学科分类号
071005 ; 0836 ; 090102 ; 100705 ;
摘要
Background: In Drosophila embryos, many biochemically and functionally unrelated transcription factors bind quantitatively to highly overlapping sets of genomic regions, with much of the lowest levels of binding being incidental, non-functional interactions on DNA. The primary biochemical mechanisms that drive these genome-wide occupancy patterns have yet to be established. Results: Here we use data resulting from the DNaseI digestion of isolated embryo nuclei to provide a biophysical measure of the degree to which proteins can access different regions of the genome. We show that the in vivo binding patterns of 21 developmental regulators are quantitatively correlated with DNA accessibility in chromatin. Furthermore, we find that levels of factor occupancy in vivo correlate much more with the degree of chromatin accessibility than with occupancy predicted from in vitro affinity measurements using purified protein and naked DNA. Within accessible regions, however, the intrinsic affinity of the factor for DNA does play a role in determining net occupancy, with even weak affinity recognition sites contributing. Finally, we show that programmed changes in chromatin accessibility between different developmental stages correlate with quantitative alterations in factor binding. Conclusions: Based on these and other results, we propose a general mechanism to explain the widespread, overlapping DNA binding by animal transcription factors. In this view, transcription factors are expressed at sufficiently high concentrations in cells such that they can occupy their recognition sequences in highly accessible chromatin without the aid of physical cooperative interactions with other proteins, leading to highly overlapping, graded binding of unrelated factors.
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页数:17
相关论文
共 108 条
[11]   Identification and analysis of functional elements in 1% of the human genome by the ENCODE pilot project [J].
Birney, Ewan ;
Stamatoyannopoulos, John A. ;
Dutta, Anindya ;
Guigo, Roderic ;
Gingeras, Thomas R. ;
Margulies, Elliott H. ;
Weng, Zhiping ;
Snyder, Michael ;
Dermitzakis, Emmanouil T. ;
Stamatoyannopoulos, John A. ;
Thurman, Robert E. ;
Kuehn, Michael S. ;
Taylor, Christopher M. ;
Neph, Shane ;
Koch, Christoph M. ;
Asthana, Saurabh ;
Malhotra, Ankit ;
Adzhubei, Ivan ;
Greenbaum, Jason A. ;
Andrews, Robert M. ;
Flicek, Paul ;
Boyle, Patrick J. ;
Cao, Hua ;
Carter, Nigel P. ;
Clelland, Gayle K. ;
Davis, Sean ;
Day, Nathan ;
Dhami, Pawandeep ;
Dillon, Shane C. ;
Dorschner, Michael O. ;
Fiegler, Heike ;
Giresi, Paul G. ;
Goldy, Jeff ;
Hawrylycz, Michael ;
Haydock, Andrew ;
Humbert, Richard ;
James, Keith D. ;
Johnson, Brett E. ;
Johnson, Ericka M. ;
Frum, Tristan T. ;
Rosenzweig, Elizabeth R. ;
Karnani, Neerja ;
Lee, Kirsten ;
Lefebvre, Gregory C. ;
Navas, Patrick A. ;
Neri, Fidencio ;
Parker, Stephen C. J. ;
Sabo, Peter J. ;
Sandstrom, Richard ;
Shafer, Anthony .
NATURE, 2007, 447 (7146) :799-816
[12]   Nucleosome retention and the stochastic nature of promoter chromatin remodeling for transcription [J].
Boeger, Hinrich ;
Griesenbeck, Joachim ;
Kornberg, Roger D. .
CELL, 2008, 133 (04) :716-726
[13]   Functional Targets of the Monogenic Diabetes Transcription Factors HNF-1α and HNF-4α Are Highly Conserved Between Mice and Humans [J].
Boj, Sylvia F. ;
Servitja, Joan Marc ;
Martin, David ;
Rios, Martin ;
Talianidis, Iannis ;
Guigo, Roderic ;
Ferrer, Jorge .
DIABETES, 2009, 58 (05) :1245-1253
[14]   Transcriptional regulatory cascades in development: Initial rates, not steady state, determine network kinetics [J].
Bolouri, H ;
Davidson, EH .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2003, 100 (16) :9371-9376
[15]   Core transcriptional regulatory circuitry in human embryonic stem cells [J].
Boyer, LA ;
Lee, TI ;
Cole, MF ;
Johnstone, SE ;
Levine, SS ;
Zucker, JR ;
Guenther, MG ;
Kumar, RM ;
Murray, HL ;
Jenner, RG ;
Gifford, DK ;
Melton, DA ;
Jaenisch, R ;
Young, RA .
CELL, 2005, 122 (06) :947-956
[16]   High-resolution mapping and characterization of open chromatin across the genome [J].
Boyle, Alan P. ;
Davis, Sean ;
Shulha, Hennady P. ;
Meltzer, Paul ;
Margulies, Elliott H. ;
Weng, Zhiping ;
Furey, Terrence S. ;
Crawford, Gregory E. .
CELL, 2008, 132 (02) :311-322
[17]   Binding Site Turnover Produces Pervasive Quantitative Changes in Transcription Factor Binding between Closely Related Drosophila Species [J].
Bradley, Robert K. ;
Li, Xiao-Yong ;
Trapnell, Cole ;
Davidson, Stuart ;
Pachter, Lior ;
Chu, Hou Cheng ;
Tonkin, Leath A. ;
Biggin, Mark D. ;
Eisen, Michael B. .
PLOS BIOLOGY, 2010, 8 (03)
[18]   The logic of chromatin architecture and remodelling at promoters [J].
Cairns, Bradley R. .
NATURE, 2009, 461 (7261) :193-198
[19]  
Campos-Ortega JA, 1997, EMBRYONIC DEV DROSOP
[20]   Genome-wide MyoD Binding in Skeletal Muscle Cells: A Potential for Broad Cellular Reprogramming [J].
Cao, Yi ;
Yao, Zizhen ;
Sarkar, Deepayan ;
Lawrence, Michael ;
Sanchez, Gilson J. ;
Parker, Maura H. ;
MacQuarrie, Kyle L. ;
Davison, Jerry ;
Morgan, Martin T. ;
Ruzzo, Walter L. ;
Gentleman, Robert C. ;
Tapscott, Stephen J. .
DEVELOPMENTAL CELL, 2010, 18 (04) :662-674