Tags

Type your tag names separated by a space and hit enter

Identifying Regulatory Pathways of SYK Expression in Human Basophils.

Abstract

BACKGROUND

Expression levels of SYK, a critical signaling tyrosine kinase in basophils, are uniquely low relative to all other circulating leukocytes and levels are highly variable in the population.

HYPOTHESIS

Transcriptional regulation of SYK through unique silencing of the SYK gene determines its basophil-specific expression patterns.

METHODS

Basophils (CD34B) were derived from cultures of CD34+ progenitor cells by two methods (G1 or G3). Peripheral blood basophils (PBB, relative SYK protein level = 1), B-cell (SYK = 8), CD34B G1 (SYK = 11) and G3 (SYK = 5) were examined by ATACseq methods and the transcriptomes of 6 cell types, PBB, eosinophils (PBE, SYK = 11), dendritic cells (PDC, SYK = 30), CD34+ progenitors (SYK = 11), CD34B G1 and G3 were analyzed for patterns that matched patterns of SYK expression in these cells, with a focus on transcription factors.

RESULTS

ATACseq showed that PBB have multiple open regions in the SYK gene suggesting a non-silenced state with: 1 region unique to PBB (low SYK expression), one region unique to both PBB (low SYK expression) and G1/G3 CD34B (high and moderate SYK expression, respectively) and 5 regions unique to B-cells (high SYK expression). SYK expression across the 6 cell types explored showed a unique pattern that was matched to the expression patterns of 3 transcription factors, KLF5, ZNF608, and c-MAF.

CONCLUSIONS

Two new potential regulatory pathways for SYK expression were identified. One appears independent of transcriptional regulation and one appears to be dependent on transcriptional control in the SYK gene.

Authors+Show Affiliations

Johns Hopkins University, Asthma and Allergy Center, Baltimore, MD 21224; Department of Laboratory Medicine, Shanghai General Hospital, Shanghai JiaoTong University School of Medicine, Shanghai, 200080, China.Laboratory of Molecular Biology and Immunology, Biomedical Research Center, National Institutes of Health/National Institute on Aging, Baltimore, MD 21224.Johns Hopkins University, Asthma and Allergy Center, Baltimore, MD 21224.Laboratory of Molecular Biology and Immunology, Biomedical Research Center, National Institutes of Health/National Institute on Aging, Baltimore, MD 21224.Johns Hopkins University, Asthma and Allergy Center, Baltimore, MD 21224. Electronic address: dmacglas@jhmi.edu.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

31629804

Citation

Peng, Xia, et al. "Identifying Regulatory Pathways of SYK Expression in Human Basophils." The Journal of Allergy and Clinical Immunology, 2019.
Peng X, Zhao M, Gao L, et al. Identifying Regulatory Pathways of SYK Expression in Human Basophils. J Allergy Clin Immunol. 2019.
Peng, X., Zhao, M., Gao, L., Sen, R., & MacGlashan, D. (2019). Identifying Regulatory Pathways of SYK Expression in Human Basophils. The Journal of Allergy and Clinical Immunology, doi:10.1016/j.jaci.2019.10.005.
Peng X, et al. Identifying Regulatory Pathways of SYK Expression in Human Basophils. J Allergy Clin Immunol. 2019 Oct 17; PubMed PMID: 31629804.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Identifying Regulatory Pathways of SYK Expression in Human Basophils. AU - Peng,Xia, AU - Zhao,Mingming, AU - Gao,Li, AU - Sen,Ranjan, AU - MacGlashan,Donald,Jr Y1 - 2019/10/17/ PY - 2019/06/17/received PY - 2019/08/27/revised PY - 2019/10/01/accepted PY - 2019/10/21/entrez PY - 2019/10/21/pubmed PY - 2019/10/21/medline KW - Allergy KW - Basophil KW - Development KW - Human KW - Signal Transduction JF - The Journal of allergy and clinical immunology JO - J. Allergy Clin. Immunol. N2 - BACKGROUND: Expression levels of SYK, a critical signaling tyrosine kinase in basophils, are uniquely low relative to all other circulating leukocytes and levels are highly variable in the population. HYPOTHESIS: Transcriptional regulation of SYK through unique silencing of the SYK gene determines its basophil-specific expression patterns. METHODS: Basophils (CD34B) were derived from cultures of CD34+ progenitor cells by two methods (G1 or G3). Peripheral blood basophils (PBB, relative SYK protein level = 1), B-cell (SYK = 8), CD34B G1 (SYK = 11) and G3 (SYK = 5) were examined by ATACseq methods and the transcriptomes of 6 cell types, PBB, eosinophils (PBE, SYK = 11), dendritic cells (PDC, SYK = 30), CD34+ progenitors (SYK = 11), CD34B G1 and G3 were analyzed for patterns that matched patterns of SYK expression in these cells, with a focus on transcription factors. RESULTS: ATACseq showed that PBB have multiple open regions in the SYK gene suggesting a non-silenced state with: 1 region unique to PBB (low SYK expression), one region unique to both PBB (low SYK expression) and G1/G3 CD34B (high and moderate SYK expression, respectively) and 5 regions unique to B-cells (high SYK expression). SYK expression across the 6 cell types explored showed a unique pattern that was matched to the expression patterns of 3 transcription factors, KLF5, ZNF608, and c-MAF. CONCLUSIONS: Two new potential regulatory pathways for SYK expression were identified. One appears independent of transcriptional regulation and one appears to be dependent on transcriptional control in the SYK gene. SN - 1097-6825 UR - https://www.unboundmedicine.com/medline/citation/31629804/Identifying_Regulatory_Pathways_of_SYK_Expression_in_Human_Basophils L2 - https://linkinghub.elsevier.com/retrieve/pii/S0091-6749(19)31324-7 DB - PRIME DP - Unbound Medicine ER -