TY - JOUR
T1 - Transcription factor, promoter, and enhancer utilization in human myeloid cells
AU - Joshi, Anagha
AU - Pooley, Christopher
AU - Freeman, Tom C.
AU - Lennartsson, Andreas
AU - Babina, Magda
AU - Schmidl, Christian
AU - Geijtenbeek, Teunis
AU - Michoel, Tom
AU - Severin, Jessica
AU - Itoh, Masayoshi
AU - Lassmann, Timo
AU - Kawaji, Hideya
AU - Hayashizaki, Yoshihide
AU - Carninci, Piero
AU - Forrest, Alistair R. R.
AU - Rehli, Michael
AU - Hume, David A.
PY - 2015
Y1 - 2015
N2 - The generation of myeloid cells from their progenitors is regulated at the level of transcription by combinatorial control of key transcription factors influencing cell-fate choice. To unravel the global dynamics of this process at the transcript level, we generated transcription profiles for 91 human cell types of myeloid origin by use of CAGE profiling. The CAGE sequencing of these samples has allowed us to investigate diverse aspects of transcription control during myelopoiesis, such as identification of novel transcription factors, miRNAs, and noncoding RNAs specific to the myeloid lineage. We further reconstructed a transcription regulatory network by clustering coexpressed transcripts and associating them with enriched cis-regulatory motifs. With the use of the bidirectional expression as a proxy for enhancers, we predicted over 2000 novel enhancers, including an enhancer 38 kb downstream of IRF8 and an intronic enhancer in the KIT gene locus. Finally, we highlighted relevance of these data to dissect transcription dynamics during progressive maturation of granulocyte precursors. A multifaceted analysis of the myeloid transcriptome is made available (www.myeloidome.roslin.ed.ac.uk). This high-quality dataset provides a powerful resource to study transcriptional regulation during myelopoiesis and to infer the likely functions of unannotated genes in human innate immunity
AB - The generation of myeloid cells from their progenitors is regulated at the level of transcription by combinatorial control of key transcription factors influencing cell-fate choice. To unravel the global dynamics of this process at the transcript level, we generated transcription profiles for 91 human cell types of myeloid origin by use of CAGE profiling. The CAGE sequencing of these samples has allowed us to investigate diverse aspects of transcription control during myelopoiesis, such as identification of novel transcription factors, miRNAs, and noncoding RNAs specific to the myeloid lineage. We further reconstructed a transcription regulatory network by clustering coexpressed transcripts and associating them with enriched cis-regulatory motifs. With the use of the bidirectional expression as a proxy for enhancers, we predicted over 2000 novel enhancers, including an enhancer 38 kb downstream of IRF8 and an intronic enhancer in the KIT gene locus. Finally, we highlighted relevance of these data to dissect transcription dynamics during progressive maturation of granulocyte precursors. A multifaceted analysis of the myeloid transcriptome is made available (www.myeloidome.roslin.ed.ac.uk). This high-quality dataset provides a powerful resource to study transcriptional regulation during myelopoiesis and to infer the likely functions of unannotated genes in human innate immunity
U2 - https://doi.org/10.1189/jlb.6TA1014-477RR
DO - https://doi.org/10.1189/jlb.6TA1014-477RR
M3 - Article
C2 - 25717144
SN - 0741-5400
VL - 97
SP - 985
EP - 995
JO - Journal of leukocyte biology
JF - Journal of leukocyte biology
IS - 5
ER -