PMID- 38348998
OWN - NLM
STAT- MEDLINE
DCOM- 20240508
LR  - 20240510
IS  - 1362-4962 (Electronic)
IS  - 0305-1048 (Print)
IS  - 0305-1048 (Linking)
VI  - 52
IP  - 8
DP  - 2024 May 8
TI  - Lineage-determining transcription factor-driven promoters regulate cell 
      type-specific macrophage gene expression.
PG  - 4234-4256
LID - 10.1093/nar/gkae088 [doi]
AB  - 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.
CI  - (c) The Author(s) 2024. Published by Oxford University Press on behalf of Nucleic 
      Acids Research.
FAU - Nagy, Gergely
AU  - Nagy G
AUID- ORCID: 0000-0002-3273-731X
AD  - Department of Biochemistry and Molecular Biology, Faculty of Medicine, University 
      of Debrecen, Debrecen, Hungary.
FAU - Bojcsuk, Dora
AU  - Bojcsuk D
AD  - Department of Biochemistry and Molecular Biology, Faculty of Medicine, University 
      of Debrecen, Debrecen, Hungary.
FAU - Tzerpos, Petros
AU  - Tzerpos P
AD  - Department of Biochemistry and Molecular Biology, Faculty of Medicine, University 
      of Debrecen, Debrecen, Hungary.
FAU - Cseh, Timea
AU  - Cseh T
AD  - Department of Biochemistry and Molecular Biology, Faculty of Medicine, University 
      of Debrecen, Debrecen, Hungary.
FAU - Nagy, Laszlo
AU  - Nagy L
AD  - Department of Biochemistry and Molecular Biology, Faculty of Medicine, University 
      of Debrecen, Debrecen, Hungary.
AD  - Departments of Medicine and Biological Chemistry, Johns Hopkins University School 
      of Medicine, Institute for Fundamental Biomedical Research, Johns Hopkins All 
      Children's Hospital, St. Petersburg, FL, USA.
LA  - eng
GR  - Nuclear Receptor Research Laboratory/
GR  - OTKA PD135102/Hungarian Scientific Research Fund/
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - Nucleic Acids Res
JT  - Nucleic acids research
JID - 0411011
RN  - 0 (Transcription Factors)
SB  - IM
MH  - *Promoter Regions, Genetic
MH  - *Macrophages/metabolism
MH  - Animals
MH  - Mice
MH  - *Transcription Factors/metabolism/genetics
MH  - *Gene Expression Regulation
MH  - *DNA Methylation
MH  - Cell Lineage/genetics
PMC - PMC11077085
EDAT- 2024/02/13 12:44
MHDA- 2024/05/08 06:45
PMCR- 2024/02/13
CRDT- 2024/02/13 08:28
PHST- 2024/01/29 00:00 [accepted]
PHST- 2024/01/18 00:00 [revised]
PHST- 2023/03/06 00:00 [received]
PHST- 2024/05/08 06:45 [medline]
PHST- 2024/02/13 12:44 [pubmed]
PHST- 2024/02/13 08:28 [entrez]
PHST- 2024/02/13 00:00 [pmc-release]
AID - 7606962 [pii]
AID - gkae088 [pii]
AID - 10.1093/nar/gkae088 [doi]
PST - ppublish
SO  - Nucleic Acids Res. 2024 May 8;52(8):4234-4256. doi: 10.1093/nar/gkae088.