Simple combinations of lineage-determining transcription factors prime cis-regulatory elements required for macrophage and B cell identities
- PMID: 20513432
- PMCID: PMC2898526
- DOI: 10.1016/j.molcel.2010.05.004
Simple combinations of lineage-determining transcription factors prime cis-regulatory elements required for macrophage and B cell identities
Abstract
Genome-scale studies have revealed extensive, cell type-specific colocalization of transcription factors, but the mechanisms underlying this phenomenon remain poorly understood. Here, we demonstrate in macrophages and B cells that collaborative interactions of the common factor PU.1 with small sets of macrophage- or B cell lineage-determining transcription factors establish cell-specific binding sites that are associated with the majority of promoter-distal H3K4me1-marked genomic regions. PU.1 binding initiates nucleosome remodeling, followed by H3K4 monomethylation at large numbers of genomic regions associated with both broadly and specifically expressed genes. These locations serve as beacons for additional factors, exemplified by liver X receptors, which drive both cell-specific gene expression and signal-dependent responses. Together with analyses of transcription factor binding and H3K4me1 patterns in other cell types, these studies suggest that simple combinations of lineage-determining transcription factors can specify the genomic sites ultimately responsible for both cell identity and cell type-specific responses to diverse signaling inputs.
Copyright 2010 Elsevier Inc. All rights reserved.
Figures
![Figure 1](https://cdn.statically.io/img/www.ncbi.nlm.nih.gov/pmc/articles/instance/2898526/bin/nihms206920f1.gif)
![Figure 2](https://cdn.statically.io/img/www.ncbi.nlm.nih.gov/pmc/articles/instance/2898526/bin/nihms206920f2.gif)
![Figure 3](https://cdn.statically.io/img/www.ncbi.nlm.nih.gov/pmc/articles/instance/2898526/bin/nihms206920f3.gif)
![Figure 4](https://cdn.statically.io/img/www.ncbi.nlm.nih.gov/pmc/articles/instance/2898526/bin/nihms206920f4.gif)
![Figure 5](https://cdn.statically.io/img/www.ncbi.nlm.nih.gov/pmc/articles/instance/2898526/bin/nihms206920f5.gif)
![Figure 6](https://cdn.statically.io/img/www.ncbi.nlm.nih.gov/pmc/articles/instance/2898526/bin/nihms206920f6.gif)
Similar articles
-
Roles of lineage-determining transcription factors in establishing open chromatin: lessons from high-throughput studies.Curr Top Microbiol Immunol. 2012;356:1-15. doi: 10.1007/82_2011_142. Curr Top Microbiol Immunol. 2012. PMID: 21744305 Review.
-
Two distinct auto-regulatory loops operate at the PU.1 locus in B cells and myeloid cells.Blood. 2011 Mar 10;117(10):2827-38. doi: 10.1182/blood-2010-08-302976. Epub 2011 Jan 14. Blood. 2011. PMID: 21239694 Free PMC article.
-
Serum response factor utilizes distinct promoter- and enhancer-based mechanisms to regulate cytoskeletal gene expression in macrophages.Mol Cell Biol. 2011 Feb;31(4):861-75. doi: 10.1128/MCB.00836-10. Epub 2010 Dec 6. Mol Cell Biol. 2011. PMID: 21135125 Free PMC article.
-
PU.1, a shared transcriptional regulator of lymphoid and myeloid cell fates.Cold Spring Harb Symp Quant Biol. 1999;64:13-20. doi: 10.1101/sqb.1999.64.13. Cold Spring Harb Symp Quant Biol. 1999. PMID: 11232277 Review. No abstract available.
-
Comparison of the expression and function of the transcription factor PU.1 (Spi-1 proto-oncogene) between murine macrophages and B lymphocytes.Oncogene. 1994 Jan;9(1):121-32. Oncogene. 1994. PMID: 8302571
Cited by
-
Mapping putative enhancers in mouse oocytes and early embryos reveals TCF3/12 as key folliculogenesis regulators.Nat Cell Biol. 2024 Jun;26(6):962-974. doi: 10.1038/s41556-024-01422-x. Epub 2024 Jun 5. Nat Cell Biol. 2024. PMID: 38839978
-
Orthogonal proteogenomic analysis identifies the druggable PA2G4-MYC axis in 3q26 AML.Nat Commun. 2024 Jun 4;15(1):4739. doi: 10.1038/s41467-024-48953-3. Nat Commun. 2024. PMID: 38834613 Free PMC article.
-
Defining cis-regulatory elements and transcription factors that control human cortical interneuron development.iScience. 2024 May 11;27(6):109967. doi: 10.1016/j.isci.2024.109967. eCollection 2024 Jun 21. iScience. 2024. PMID: 38827400 Free PMC article.
-
Predicting gene expression state and prioritizing putative enhancers using 5hmC signal.Genome Biol. 2024 Jun 3;25(1):142. doi: 10.1186/s13059-024-03273-z. Genome Biol. 2024. PMID: 38825692 Free PMC article.
-
Native and tagged CENP-A histones are functionally inequivalent.Epigenetics Chromatin. 2024 Jun 2;17(1):19. doi: 10.1186/s13072-024-00543-9. Epigenetics Chromatin. 2024. PMID: 38825690 Free PMC article.
References
-
- Adolfsson J, Mansson R, Buza-Vidas N, Hultquist A, Liuba K, Jensen CT, Bryder D, Yang L, Borge OJ, Thoren LA, et al. Identification of Flt3+ lympho-myeloid stem cells lacking erythro-megakaryocytic potential a revised road map for adult blood lineage commitment. Cell. 2005;121:295–306. - PubMed
-
- Barski A, Cuddapah S, Cui K, Roh TY, Schones DE, Wang Z, Wei G, Chepelev I, Zhao K. High-resolution profiling of histone methylations in the human genome. Cell. 2007;129:823–837. - PubMed
Publication types
MeSH terms
Substances
Associated data
- Actions
Grants and funding
- P30 DK063491-039003/DK/NIDDK NIH HHS/United States
- R01 CA052599-19/CA/NCI NIH HHS/United States
- U19 DK062434-080007/DK/NIDDK NIH HHS/United States
- P30 DK063491-029003/DK/NIDDK NIH HHS/United States
- U19 DK062434-060007/DK/NIDDK NIH HHS/United States
- U19 DK062434/DK/NIDDK NIH HHS/United States
- R01 CA052599-20/CA/NCI NIH HHS/United States
- P30 DK063491/DK/NIDDK NIH HHS/United States
- R01 CA054198/CA/NCI NIH HHS/United States
- R01 CA052599-17/CA/NCI NIH HHS/United States
- R01 CA052599-18/CA/NCI NIH HHS/United States
- R01 CA078384/CA/NCI NIH HHS/United States
- P50 GM081892-01A1/GM/NIGMS NIH HHS/United States
- P50 GM081892/GM/NIGMS NIH HHS/United States
- HC088093/HC/NHLBI NIH HHS/United States
- F32 HL083752/HL/NHLBI NIH HHS/United States
- R01 CA052599/CA/NCI NIH HHS/United States
- R01 DK091183/DK/NIDDK NIH HHS/United States
- P30 DK063491-019003/DK/NIDDK NIH HHS/United States
- U19 DK062434-08S10007/DK/NIDDK NIH HHS/United States
- P30 DK063491-049003/DK/NIDDK NIH HHS/United States
- DK62434/DK/NIDDK NIH HHS/United States
- DK063491/DK/NIDDK NIH HHS/United States
- CA52599/CA/NCI NIH HHS/United States
- U19 DK062434-070007/DK/NIDDK NIH HHS/United States
LinkOut - more resources
Full Text Sources
Other Literature Sources
Molecular Biology Databases