3 research outputs found
The SWI/SNF ATP-Dependent Chromatin Remodeling Complex in Arabidopsis Responds to Environmental Changes in Temperature-Dependent Manner
SWI/SNF ATP-dependent chromatin remodeling complexes (CRCs) play important roles in the regulation of transcription, cell cycle, DNA replication, repair, and hormone signaling in eukaryotes. The core of SWI/SNF CRCs composed of a SWI2/SNF2 type ATPase, a SNF5 and two of SWI3 subunits is sufficient for execution of nucleosome remodeling in vitro. The Arabidopsis genome encodes four SWI2/SNF2 ATPases, four SWI3, a single SNF5 and two SWP73 subunits. Genes of the core SWI/SNF components have critical but not fully overlapping roles during plant growth, embryogenesis, and sporophyte development. Here we show that the Arabidopsis swi3c mutant exhibits a phenotypic reversion when grown at lower temperature resulting in partial restoration of its embryo, root development and fertility defects. Our data indicates that the swi3c mutation alters the expression of several genes engaged in low temperature responses. The location of SWI3C-containing SWI/SNF CRCs on the ICE1, MYB15 and CBF1 target genes depends on the temperature conditions, and the swi3c mutation thus also influences the transcription of several cold-responsive (COR) genes. These findings, together with genetic analysis of swi3c/ice1 double mutant and enhanced freezing tolerance of swi3c plants illustrate that SWI/SNF CRCs contribute to fine-tuning of plant growth responses to different temperature regimes
PD-L1 Overexpression, SWI/SNF Complex Deregulation, and Profound Transcriptomic Changes Characterize Cancer-Dependent Exhaustion of Persistently Activated CD4+ T Cells
Growing tumors avoid recognition and destruction by the immune system. During
continuous stimulation of tumor-infiltrating lymphocytes (TILs) by tumors, TILs become functionally
exhausted; thus, they become unable to kill tumor cells and to produce certain cytokines and lose
their ability to proliferate. This collectively results in the immune escape of cancer cells. Here, we
show that breast cancer cells expressing PD-L1 can accelerate exhaustion of persistently activated
human effector CD4+ T cells, manifesting in high PD-1 and PD-L1 expression level son T cell surfaces,
decreased glucose metabolism genes, strong downregulation of SWI/SNF chromatin remodelingcomplex subunits, and p21 cell cycle inhibitor upregulation. This results in inhibition of T cell
proliferation and reduction of T cell numbers. The RNAseq analysis on exhausted CD4+ T cells
indicated strong overexpression of IDO1 and genes encoding pro-inflammatory cytokines and
chemokines. Some interleukins were also detected in media from CD4+ T cells co-cultured with
cancer cells. The PD-L1 overexpression was also observed in CD4+ T cells after co-cultivation with
other cell lines overexpressing PD-L1, which suggested the existence of a general mechanism of CD4+
T cell exhaustion induced by cancer cells. The ChIP analysis on the PD-L1 promoter region indicated
that the BRM recruitment in control CD4+ T cells was replaced by BRG1 and EZH2 in CD4+ T cells
strongly exhausted by cancer cells. These findings suggest that epi-drugs such as EZH2 inhibitors
may be used as immunomodulators in cancer treatment
A non-canonical function of Arabidopsis ERECTA proteins and a role of the SWI3B subunit of the SWI/SNF chromatin remodeling complex in gibberellin signaling
The Arabidopsis ERECTA family (ERf) of leucine-rich repeat receptor-like kinases (LRR-RLKs) comprising
ERECTA (ER), ERECTA-LIKE 1 (ERL1), and ERECTA-LIKE 2 (ERL2) controls epidermal patterning, inflorescence
architecture, and stomata development and patterning. These proteins are reported to be plasma membrane associated. Here we show that the er/erl1/erl2 mutant exhibits impaired gibberellin (GA) biosynthesis
and perception alongside broad transcriptional changes. The ERf kinase domains were found to localize to
the nucleus where they interact with the SWI3B subunit of the SWI/SNF chromatin remodeling complex
(CRCs). The er/erl1/erl2 mutant exhibits reduced SWI3B protein level and affected nucleosomal chromatin
structure. Similar to swi3c and brm plants with inactivated subunits of SWI/SNF CRCs, it also does not
accumulate DELLA RGA and GAI proteins. The ER kinase phosphorylates SWI3B in vitro, and the inactiva�tion of all ERf proteins leads to the decreased phosphorylation of SWI3B protein in vivo. The identified cor�relation between DELLA overaccumulation and SWI3B proteasomal degradation, and the physical
interaction of SWI3B with DELLA proteins indicate an important role of SWI3B-containing SWI/SNF CRCs in
gibberellin signaling. Co-localization of ER and SWI3B on GID1 (GIBBERELLIN INSENSITIVE DWARF 1)
DELLA target gene promoter regions and abolished SWI3B binding to GID1 promoters in er/erl1/erl2 plants
supports the conclusion that ERf-SWI/SNF CRC interaction is important for transcriptional control of GA
receptors. Thus, the involvement of ERf proteins in the transcriptional control of gene expression, and
observed similar features for human HER2 (epidermal growth family receptor member), indicate an exciting
target for further studies of evolutionarily conserved non-canonical functions of eukaryotic membrane
receptors