Evidence map›Paper›PMID 17116688›Full record

ArticleMolecular and cellular biology2007

A two-step, PU.1-dependent mechanism for developmentally regulated chromatin remodeling and transcription of the c-fms gene.

Hanna Krysinska, Maarten Hoogenkamp, Richard Ingram, Nicola Wilson, Hiromi Tagoh, Peter Laslo, Harinder Singh, Constanze Bonifer

Open access · bronzeAbstract read
In one paragraph

Article in Molecular and cellular biology, 2007. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 46 papers.

0numbers the graph read from it
0cells of the map it votes in
46citing papers in PubMed
3.1field-weighted citation impact, top 8% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

46 citing papers in PubMed, 100 citations in OpenAlex.

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  14. Logical modeling of lymphoid and myeloid cell specification and transdifferentiation.Proceedings of the National Academy of Sciences of the United States of America · 2017
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  18. Amphibian macrophage development and antiviral defenses.Developmental and comparative immunology · 2016
    Review
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

8 authors at 4 institutions in 2 countries.

Hanna KrysinskaUniversity of Leeds, Leeds Institute of Molecular Medicine, St. James's University Hospital, Wellcome Trust Brenner Building, Leeds LS9 7TF, United Kingdom.
Maarten Hoogenkamp
Richard Ingram
Nicola Wilson
Hiromi Tagoh
Peter Laslo
Harinder Singh
Constanze Bonifer
St James's University Hospital · GBUniversity of Leeds · GBHoward Hughes Medical Institute · USUniversity of Chicago · US

Funding

Biotechnology and Biological Sciences Research Council BBS/B/07438Biotechnology and Biological Sciences Research Council G18655
6 · The paper itself

Abstract

Hematopoietic stem cells and multipotent progenitors exhibit low-level transcription and partial chromatin reorganization of myeloid cell-specific genes including the c-fms (csf1R) locus. Expression of the c-fms gene is dependent on the Ets family transcription factor PU.1 and is upregulated during myeloid differentiation, enabling committed macrophage precursors to respond to colony-stimulating factor 1. To analyze molecular mechanisms underlying the transcriptional priming and developmental upregulation of the c-fms gene, we have utilized myeloid progenitors lacking the transcription factor PU.1. PU.1 can bind to sites in both the c-fms promoter and the c-fms intronic regulatory element (FIRE enhancer). Unlike wild-type progenitors, the PU.1(-/-) cells are unable to express c-fms or initiate macrophage differentiation. When PU.1 was reexpressed in mutant progenitors, the chromatin structure of the c-fms promoter was rapidly reorganized. In contrast, assembly of transcription factors at FIRE, acquisition of active histone marks, and high levels of c-fms transcription occurred with significantly slower kinetics. We demonstrate that the reason for this differential activation was that PU.1 was required to promote induction and binding of a secondary transcription factor, Egr-2, which is important for FIRE enhancer activity. These data suggest that the c-fms promoter is maintained in a primed state by PU.1 in progenitor cells and that at FIRE PU.1 functions with another transcription factor to direct full activation of the c-fms locus in differentiated myeloid cells. The two-step mechanism of developmental gene activation that we describe here may be utilized to regulate gene activity in a variety of developmental pathways.

Indexed as

Chromatin Assembly and DisassemblyGene Expression Regulation, DevelopmentalAnimalsBase SequenceDeoxyribonuclease IEarly Growth Response Protein 2Enhancer Elements, GeneticGenes, fmsHistonesKineticsMethylationMiceModels, GeneticMolecular Sequence DataNIH 3T3 CellsPromoter Regions, GeneticDeoxyribonuclease IEarly Growth Response Protein 2HistonesProto-Oncogene ProteinsProto-Oncogene Protein Spi-1RNA Polymerase IITATA-Box Binding ProteinTrans-ActivatorsTranscription Factors

Identifiers

PMID17116688
PMCPMC1800675
OpenAlexW2170487338

What OpenQuestion holds

Textmetadata
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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.