PMID- 33289106 OWN - NLM STAT- Publisher LR - 20240222 IS - 1938-3673 (Electronic) IS - 0741-5400 (Linking) DP - 2020 Dec 2 TI - Comparison of the PU.1 transcriptional regulome and interactome in human and mouse inflammatory dendritic cells. LID - 10.1002/JLB.6A1219-711RRR [doi] AB - Dendritic cells (DCs) are key immune modulators and are able to mount immune responses or tolerance. DC differentiation and activation imply a plethora of molecular and cellular responses, including transcriptional changes. PU.1 is a highly expressed transcription factor in DCs and coordinates relevant aspects of DC biology. Due to their role as immune regulators, DCs pose as a promising immunotherapy tool. However, some of their functional features, such as survival, activation, or migration, are compromised due to the limitations to simulate in vitro the physiologic DC differentiation process. A better knowledge of transcriptional programs would allow the identification of potential targets for manipulation with the aim of obtaining "qualified" DCs for immunotherapy purposes. Most of the current knowledge regarding DC biology derives from studies using mouse models, which not always find a parallel in human. In the present study, we dissect the PU.1 transcriptional regulome and interactome in mouse and human DCs, in the steady state or LPS activated. The PU.1 transcriptional regulome was identified by performing PU.1 chromatin immunoprecipitation followed by high-throughput sequencing and pairing these data with RNAsequencing data. The PU.1 interactome was identified by performing PU.1 immunoprecipitation followed by mass spectrometry analysis. Our results portray PU.1 as a pivotal factor that plays an important role in the regulation of genes required for proper DC activation and function, and assures the repression of nonlineage genes. The interspecies differences between human and mouse DCs are surprisingly substantial, highlighting the need to study the biology of human DCs. CI - (c)2020 Society for Leukocyte Biology. FAU - Scheenstra, Maaike R AU - Scheenstra MR AD - Department of Blood Cell Research, Sanquin Research and Landsteiner Laboratory, Academic Medical Center (AMC), University of Amsterdam, Amsterdam, The Netherlands. AD - Division of Infectious Diseases and Immunology, Department of Biomolecular Health Sciences, Utrecht University, Utrecht, The Netherlands. FAU - Martinez-Botia, Patricia AU - Martinez-Botia P AD - Instituto de Investigacion Sanitaria del Principado de Asturias (ISPA), Oviedo, Spain. FAU - Acebes-Huerta, Andrea AU - Acebes-Huerta A AD - Instituto de Investigacion Sanitaria del Principado de Asturias (ISPA), Oviedo, Spain. FAU - Brouwer, Rutger W W AU - Brouwer RWW AD - Center for Biomics, Erasmus MC, Rotterdam, The Netherlands. AD - Department of Cell Biology, Erasmus MC, Rotterdam, The Netherlands. FAU - Caballero-Sanchez, Noemi AU - Caballero-Sanchez N AD - Instituto de Investigacion Sanitaria del Principado de Asturias (ISPA), Oviedo, Spain. FAU - Gillemans, Nynke AU - Gillemans N AD - Department of Cell Biology, Erasmus MC, Rotterdam, The Netherlands. FAU - De Bleser, Pieter AU - De Bleser P AD - Department of Biomedical Molecular Biology, Ghent University, Ghent, Belgium. AD - VIB Center for Inflammation Research, Data Mining and Modeling for Biomedicine, Ghent, Belgium. FAU - Nota, Benjamin AU - Nota B AD - Department of Blood Cell Research, Sanquin Research and Landsteiner Laboratory, Academic Medical Center (AMC), University of Amsterdam, Amsterdam, The Netherlands. FAU - De Cuyper, Iris M AU - De Cuyper IM AD - Department of Blood Cell Research, Sanquin Research and Landsteiner Laboratory, Academic Medical Center (AMC), University of Amsterdam, Amsterdam, The Netherlands. FAU - Salunkhe, Vishal AU - Salunkhe V AD - Department of Blood Cell Research, Sanquin Research and Landsteiner Laboratory, Academic Medical Center (AMC), University of Amsterdam, Amsterdam, The Netherlands. FAU - Woltman, Andrea M AU - Woltman AM AD - Department of Gastroenterology and Hepatology, Erasmus MC, Rotterdam, The Netherlands. AD - Current Address: Institute of Medical Education Research Rotterdam, Erasmus MC, Rotterdam, The Netherlands. FAU - van de Laar, Lianne AU - van de Laar L AD - Department of Gastroenterology and Hepatology, Erasmus MC, Rotterdam, The Netherlands. FAU - Rijkers, Erikjan AU - Rijkers E AD - Proteomics Center, Erasmus MC, Rotterdam, The Netherlands. FAU - Demmers, Jeroen A A AU - Demmers JAA AD - Proteomics Center, Erasmus MC, Rotterdam, The Netherlands. FAU - van IJcken, Wilfred F J AU - van IJcken WFJ AUID- ORCID: 0000-0002-0421-8301 AD - Center for Biomics, Erasmus MC, Rotterdam, The Netherlands. AD - Department of Cell Biology, Erasmus MC, Rotterdam, The Netherlands. FAU - Philipsen, Sjaak AU - Philipsen S AD - Department of Cell Biology, Erasmus MC, Rotterdam, The Netherlands. FAU - van den Berg, Timo K AU - van den Berg TK AD - Department of Blood Cell Research, Sanquin Research and Landsteiner Laboratory, Academic Medical Center (AMC), University of Amsterdam, Amsterdam, The Netherlands. FAU - Kuijpers, Taco W AU - Kuijpers TW AD - Department of Blood Cell Research, Sanquin Research and Landsteiner Laboratory, Academic Medical Center (AMC), University of Amsterdam, Amsterdam, The Netherlands. AD - Laboratory of Immunotherapy, Sanquin Research and Landsteiner Laboratory, Amsterdam University Medical Center, University of Amsterdam, Amsterdam, The Netherlands. AD - Department of Molecular Cell Biology and Immunology, Amsterdam University Medical Center, Vrije University, Amsterdam, The Netherlands. FAU - Gutierrez, Laura AU - Gutierrez L AUID- ORCID: 0000-0001-8443-900X AD - Department of Blood Cell Research, Sanquin Research and Landsteiner Laboratory, Academic Medical Center (AMC), University of Amsterdam, Amsterdam, The Netherlands. AD - Instituto de Investigacion Sanitaria del Principado de Asturias (ISPA), Oviedo, Spain. AD - University of Oviedo, Oviedo, Spain. LA - eng GR - VENI 863.09.012/Netherlands Scientific Organization/ GR - RYC-2013-12587/Spanish Ministerio de Economia y Competitividad/ GR - PA-20-PF-BP19-014/Co nsejeria de Ciencia, Innovacion y Universidad del Principado de Asturias (Spain)/ GR - Fundacion para la Investigacion y la Innovacion Biosanitaria de Asturias (FINBA, Spain)/ PT - Journal Article DEP - 20201202 PL - England TA - J Leukoc Biol JT - Journal of leukocyte biology JID - 8405628 SB - IM OTO - NOTNLM OT - PU.1 OT - dendritic cells OT - interactome OT - interspecies OT - transcription factor OT - transcriptome EDAT- 2020/12/09 06:00 MHDA- 2020/12/09 06:00 CRDT- 2020/12/08 05:46 PHST- 2019/12/11 00:00 [received] PHST- 2020/11/18 00:00 [revised] PHST- 2020/11/18 00:00 [accepted] PHST- 2020/12/08 05:46 [entrez] PHST- 2020/12/09 06:00 [pubmed] PHST- 2020/12/09 06:00 [medline] AID - 10.1002/JLB.6A1219-711RRR [doi] PST - aheadofprint SO - J Leukoc Biol. 2020 Dec 2. doi: 10.1002/JLB.6A1219-711RRR.