The role of chromatin accessibility in directing the widespread, overlapping patterns of Drosophila transcription factor binding
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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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Other RFX members have been demonstrated to regulate MHC class II expression.
“as other RFX members have been demonstrated to regulate MHC class II expression 35,64”
From Type 1 interferon perturbates clonal competition by reshaping human blood development (2026) · cites this paper as [64]
Our copy’s Discussion addresses chromatin accessibility and transcription-factor binding in Drosophila, not regulation of MHC class II expression. Searches for RFX, MHC class II, and major histocompatibility complex found no passage addressing the claim. (LLM, conf=0.75)
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Lama, C., Isakov, D., Rosenberg, S., Quijada-Álamo, M., Saurty-Seerunghen, M. S., Moein, S., Nozais, M., Abera, T.-A., Sakaguchi, O., Totwani, M., et al. (2026) · Nature Genetics · doi:10.1038/s41588-026-02751-3 · Cited by 3 · see citing works
- Authors
- Li, X.-Y., Thomas, S., Sabo, P. J., Eisen, M. B., Stamatoyannopoulos, J. A., & Biggin, M. D.
- Affiliations
- University of Washington (US)
- Howard Hughes Medical Institute (US)
- Lawrence Berkeley National Laboratory (US)
- Corresponding author
- Stamatoyannopoulos, John A
- Biggin, Mark D
- Venue
- Genome Biology
- Published
- 2011-04-07
- Volume
- 12
- Issue
- 4
- Pages
- R34-R34
- ISSN
- 1465-6906 (ISSN-L)
- 1474-760X
- PMC
- PMC3218860
- OpenAlex
- W2155718935
- Cited by
- 217
- References
- 6
- Citations by year
- 2026: 3 · 2025: 5 · 2024: 10 · 2023: 7 · 2022: 8 · 2021: 17 · 2020: 18 · 2019: 10 · 2018: 11 · 2017: 17 · 2016: 13 · 2015: 13 · 2014: 20 · 2013: 26 · 2012: 25
- FWCI
- 10.84
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- Genome biology (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- OSTI OAI (U.S. Department of Energy Office of Scientific and Technical Information) (submittedVersion)
- eScholarship (California Digital Library) (submittedVersion)
- Funders
- U.S. Department of Energy (-AC02-05CH11231, 05CH11231, DE AC02 05CH11231, DE-AC02-)
- National Institutes of Health (DE-AC02–05CH11231, 5t90hg004007-05)
- National Human Genome Research Institute (T90 HG 004007-04)
- National Institute of General Medical Sciences (GM704403, R01GM071923, R01GM070444)
- Lawrence Berkeley National Laboratory (AC02‐05CH11231, DE-AC02-05CH11231, 05CH11231)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Chromatin Remodeling and Cancer
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Diffusion and Search Dynamics
- Keywords
- chromatin accessibility, transcription factor binding, Drosophila embryo, DNase I footprinting, developmental regulators, transcriptional regulation
- MeSH terms
- Animals, Base Sequence, Binding Sites, Cell Nucleus, Chromatin, Deoxyribonuclease I, DNA, DNA-Binding Proteins, Drosophila melanogaster, Models, Genetic, Protein Binding, Transcription Factors, Computational Biology, Chromatin Immunoprecipitation, Genome, Insect
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