Helen Chen
Research Subjects
Research Interests
Helen Chen has a total of 4 co-authors. Here are the top co-authors by number of shared publications:
- Betty Diamond
Center of Autoimmune Musculoskeletal and Hematopoietic Diseases, The Feinstein Institutes for Medical Research, Northwell Health, Manhasset, New York, USA
1 shared publication Peter K. Gregersen
Center for Genomics and Human Genetics, The Feinstein Institute for Medical Research, Manhasset, New York, New York, USA
1 shared publication- Su Hwa Jang
Department of Biomedical Science, Graduate School of Biomedical Sciences and Engineering, Hanyang University, Seoul, South Korea
1 shared publication - Sun Jung Kim
Center for Autoimmune, Musculoskeletal and Hematopoietic Disease, The Feinstein Institutes for Medical Research, Northwell Health, Manhasset, New York, USA
1 shared publication
Latest Publications
- Open Access
- 12 January 2017
- Published by American Society for Clinical Investigation in JCI Insight
- Vol. 2 (1) , e89569
Kruppel-like factor4 regulates PRDM1 expression through binding to an autoimmune risk allele
A SNP identified as rs548234, which is found in PRDM1 , the gene that encodes BLIMP1, is a risk allele associated with systemic lupus erythematosus (SLE). BLIMP1 expression was reported to be decreased in women with the PRDM1 rs548234 risk allele compared with women with the nonrisk allele in monocyte-derived DCs (MO-DCs). In this study, we demonstrate that BLIMP1 expression is regulated by the binding of Kruppel-like factor 4 (KLF4) to the risk SNP. KLF4 is highly expressed in MO-DCs but undetectable in B cells, consistent with the lack of altered expression of BLIMP1 in B cells from risk SNP carriers. Female rs548234 risk allele carriers, but not nonrisk allele carriers, exhibited decreased levels of BLIMP1 in MO-DCs, showing that the regulatory function of KLF4 is influenced by the risk allele. In addition, KLF4 directly recruits histone deacetylases (HDAC4, HDAC6, and HDAC7), established negative regulators of gene expression. Finally, the knock down of KLF4 expression reversed the inhibitory effects of the risk SNP on promoter activity and BLIMP1 expression. Therefore, the binding of KLF4 and the subsequent recruitment of HDACs represent a mechanism for reduced BLIMP1 expression in MO-DCs bearing the SLE risk allele rs548234.
- 12 January 2017
- Published by American Society for Clinical Investigation in JCI Insight
- Vol. 2 (1) , e89569
Open AccessKruppel-like factor4 regulates PRDM1 expression through binding to an autoimmune risk allele
A SNP identified as rs548234, which is found in PRDM1 , the gene that encodes BLIMP1, is a risk allele associated with systemic lupus erythematosus (SLE). BLIMP1 expression was reported to be decreased in women with the PRDM1 rs548234 risk allele compared with women with the nonrisk allele in monocyte-derived DCs (MO-DCs). In this study, we demonstrate that BLIMP1 expression is regulated by the binding of Kruppel-like factor 4 (KLF4) to the risk SNP. KLF4 is highly expressed in MO-DCs but undetectable in B cells, consistent with the lack of altered expression of BLIMP1 in B cells from risk SNP carriers. Female rs548234 risk allele carriers, but not nonrisk allele carriers, exhibited decreased levels of BLIMP1 in MO-DCs, showing that the regulatory function of KLF4 is influenced by the risk allele. In addition, KLF4 directly recruits histone deacetylases (HDAC4, HDAC6, and HDAC7), established negative regulators of gene expression. Finally, the knock down of KLF4 expression reversed the inhibitory effects of the risk SNP on promoter activity and BLIMP1 expression. Therefore, the binding of KLF4 and the subsequent recruitment of HDACs represent a mechanism for reduced BLIMP1 expression in MO-DCs bearing the SLE risk allele rs548234.