Journal Article10.1093/nar/gkae088
Lineage-determining transcription factor-driven promoters regulate cell type-specific macrophage gene expression.
Gergely G. Nagy,Dóra Bojcsuk,Petros Tzerpos,Timea Cseh,László Nagy +4 more
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TL;DR: This work characterized the macrophage-specific direct DNA-TF interactions, and concludes that this unusual class of promoters regulates cell type-specific gene expression in macrophages, and such a mechanism might exist in other cell types too.
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Abstract: Mammalian promoters consist of multifarious elements, which make them unique and support the selection of the proper transcript variants required under diverse conditions in distinct cell types. However, their direct DNA-transcription factor (TF) interactions are mostly unidentified. Murine bone marrow-derived macrophages (BMDMs) are a widely used model for studying gene expression regulation. Thus, this model serves as a rich source of various next-generation sequencing data sets, including a large number of TF cistromes. By processing and integrating the available cistromic, epigenomic and transcriptomic data from BMDMs, we characterized the macrophage-specific direct DNA-TF interactions, with a particular emphasis on those specific for promoters. Whilst active promoters are enriched for certain types of typically methylatable elements, more than half of them contain non-methylatable and prototypically promoter-distal elements. In addition, circa 14% of promoters-including that of Csf1r-are composed exclusively of 'distal' elements that provide cell type-specific gene regulation by specialized TFs. Similar to CG-rich promoters, these also contain methylatable CG sites that are demethylated in a significant portion and show high polymerase activity. We conclude that this unusual class of promoters regulates cell type-specific gene expression in macrophages, and such a mechanism might exist in other cell types too.
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Citations
The role(s) of NF-Y in development and differentiation
Diletta Dolfini,Carol Imbriano,Roberto Mantovani +2 more
TL;DR: NF-Y, a conserved trimeric transcription factor, plays crucial roles in development and differentiation across various stages, from pre-implantation embryo to terminally differentiated tissues, with distinct isoforms influencing stemness and TF interactions.
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Macrophage niche imprinting as a determinant of macrophage identity and function
Malgorzata Kloc,Marta Halasa,Rafik M. Ghobrial +2 more
TL;DR: This review gives examples of macrophage niches and the modes of communication between macrophages and surrounding cells and describes how macrophages, acting against their immune defensive nature, can create a hospitable niche for pathogens and cancer cells.
Genetic variation in IL-4 activated tissue resident macrophages determines strain-specific synergistic responses to LPS epigenetically
mingming zhao,Dragana Janković,Verena M. Link,Camila Oliveira Silva Souza,Katherine M. Hornick,Oyebola O. Oyesola,Yasmine Belkaid,Justin Lack,P’ng Loke +8 more
TL;DR: Genetic variation in IL-4 activated tissue-resident macrophages from C57BL/6 and BALB/c strains determines strain-specific synergistic responses to LPS through epigenetic reprogramming, with C57BL/6 showing augmented synergy despite BALB/c displaying a more robust transcriptional response to LPS.
Roles of transposable elements and DNA methylation in the formation of CpG islands and CpG-depleted regulatory elements
Jueng Soo You,Steve Pierce,Gangning Liang,Peter A. Jones,Jueng Soo You,Steve Pierce,Gangning Liang,Peter A. Jones +7 more
Abstract: The origins of CpG islands (CGIs) are not known. They are relatively short GC-rich regions of DNA with a higher-than-expected occurrence of CpG dinucleotides compared to most of the genome. They constitute less than 1% of the human genome but harbor approximately 40% of all transcription start sites (TSSs). CGIs are usually modulated by histone modifications in somatic cells or, in a minority of cases, permanently silenced by CpG methylation. Those that do not have TSSs are called “orphan CGIs”. Here, we show that CGIs containing TSSs almost never contain any of three major classes of transposable elements (TEs) and orphan CGIs rarely do. We hypothesize that CGIs persist across evolutionary time due to counterselection against TE insertion in the germ line. The 99% of the vertebrate genome, which is not CG rich, contains 60% of TSSs and putative enhancers. We postulate that conversion of an ancestral CpG-rich genome into the current CpG-depleted version present in vertebrates may also have allowed reversible DNA methylation to function in complex and dynamic gene control circuits. Therefore, we propose an evolutionary model in which vertebrate TEs are indirectly responsible for the existence of CGIs, and the formation of regulatory elements such as TSSs and enhancers that can potentially utilize dynamic DNA methylation for gene control.
Genome-Wide Identification and Expression Analysis of the STAT Family in Reeve’s Turtle (Mauremys reevesii)
Yi Song,Zhengkui Zhou,Shichen Huang,Zhiyuan Li,Xing‐Quan Zhu,Hongming Zhou,Yuxin Jiang,Duminda S. B. Dissanayake,Arthur Georges,Ligen Xiong +9 more
TL;DR: Genome-Wide Identification and Expression Analysis of the STAT Family in Reeve’s Turtle (Mauremys reevesii) identifies Stat genes and their expression patterns in the immune system of the turtle.
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