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Bryant, B.

Publications and source records attributed to Bryant, B..

2 recordsLinked to original sources

Expression of Lysyl Oxidase Family Enzymes During Human Endometrial Decidualization

Lysyl oxidases (LOXs), comprising lysyl oxidase (LOX) and lysyl oxidase like 1-4 (LOXL1-4), constitute a highly conserved enzyme family. Their primary function is the crosslinking of collagen and elastic fibers, thereby modulating the structure and function of the extracellular matrix. Our primary objective was to elucidate the localization of LOXs within human endometrial tissues and to investigate the expression profile of LOXs during in vitro human endometrial stromal cell decidualization. Immunohistochemical localization revealed that all LOXs were expressed in human endometrium during both the proliferative and secretory phases of menstrual cycle. All five LOXs were expressed in human endometrial stromal cells cultured in vitro. Gene expression levels of LOX, LOXL1, and LOXL2 significantly decreased during endometrial stromal cell decidualization in vitro. In contrast, LOXL3 and LOXL4 gene expression remained unaffected. Protein levels of LOX, LOXL1, and LOXL3 also showed a significant reduction. Additionally, conditioned media analysis revealed abundant secretion and release of LOX and LOXL1-3 into the extracellular space at all time points examined, with their levels remaining constant. The primary targets of LOXs, collagen and elastic fibers, undergo significant synthesis and processing during endometrial stromal cell decidualization in vitro. This observation was supported by the differential gene expression levels of factors involved in their processing and assembly. Collectively, this study demonstrates the expression of LOXs in the human endometrium and their potential role in extracellular matrix reorganization during decidualization.

cell biology↗

EZH2 inhibition results in genome-wide PRC2 redistribution

Histone methyltransferase polycomb repressive complex 2 (PRC2) plays a critical role in cell fate determination, and its catalytic subunit EZH2 is a key oncogenic driver in GCB-DLBCL. EZH2 inhibition in some GCB-DLBCL cell models leads to a global loss of H3K27me3, the derepression of a subset of silenced PRC2 target genes, and ultimately cell death. Here we show that EZH2 inhibition causes global redistribution of PRC2 components. We observe a reduction in the already-low levels of PRC2 at active genes. On the other hand, focal PRC2 accumulation and concomitant H3K27me3 retention occur at many canonical embryonic stem cell PRC2 nucleation sites. PRC2 accumulation is also enriched in plasma/memory cell genes repressed by PRC2 activity in the germinal center. We see PRC2 redistribution to, and H3K27me3 retention at, differentiation-related genes not only in cell lines that are insensitive to killing by EZH2 inhibition, but also in sensitive cell lines. Thus, PRC2 redistribution to B cell differentiation genes is not sufficient to explain the resistance to EZH2 inhibitors in some DLBCL cell lines.

genomics↗