PXDN as a pan-cancer biomarker and promotes tumor progress via immune inhibition in nasopharyngeal carcinoma.

Background: Investigating oncogenes and the mechanisms driving oncogenic processes in human tumors is imperative for the development of efficient therapies. Peroxidasin (PXDN) has been reported to play a critical role in tissue development and homeostasis. However, the role of PXDN in the occurrence and development of Nasopharyngeal Carcinoma (NPC) remains unknown.

Regulation of the actin-activated MgATPase activity of Acanthamoeba myosin II by phosphorylation of serine 639 in motor domain loop 2.

It had been proposed previously that only filamentous forms of Acanthamoeba myosin II have actin-activated MgATPase activity and that this activity is inhibited by phosphorylation of up to four serine residues in a repeating sequence in the C-terminal nonhelical tailpiece of the two heavy chains. We have reinvestigated these issues using recombinant WT and mutant myosins. Contrary to the earlier proposal, we show that two nonfilamentous forms of Acanthamoeba myosin II, heavy meromyosin and myosin subfragment 1, have actin-activated MgATPase that is down-regulated by phosphorylation.

SATB1-mediated functional packaging of chromatin into loops.

Mammalian genomes are organized into multiple layers of higher-order chromatin structure, and in this organization chromatin looping is a striking and crucial feature that brings together distal genomic loci into close spatial proximity. Such three-dimensional organization of chromatin has been suggested to be functionally important in gene regulation. Many important questions need to be addressed, such as what types of nuclear proteins are responsible for folding chromatin into loops, whether there are any genomic marks that serve as the core sites of chromatin folding events, how distal genomic sites are brought together, and what are the biological consequences for interactions between distal genomic loci.

SATB1 packages densely looped, transcriptionally active chromatin for coordinated expression of cytokine genes.

SATB1 (special AT-rich sequence binding protein 1) organizes cell type-specific nuclear architecture by anchoring specialized DNA sequences and recruiting chromatin remodeling factors to control gene transcription. We studied the role of SATB1 in regulating the coordinated expression of Il5, Il4 and Il13, located in the 200-kb T-helper 2 (T(H)2) cytokine locus on mouse chromosome 11. We show that on T(H)2 cell activation, SATB1 expression is rapidly induced to form a unique transcriptionally active chromatin structure at the cytokine locus.

Loss of silent-chromatin looping and impaired imprinting of DLX5 in Rett syndrome.

Mutations in MECP2 are associated with Rett syndrome, an X-linked neurodevelopmental disorder. To identify genes targeted by Mecp2, we sequenced 100 in vivo Mecp2-binding sites in mouse brain. Several sequences mapped to an imprinted gene cluster on chromosome 6, including Dlx5 and Dlx6, whose transcription was roughly two times greater in brains of Mecp2-null mice compared with those of wild-type mice.

Tissue-specific nuclear architecture and gene expression regulated by SATB1.

Eukaryotic chromosomes are packaged in nuclei by many orders of folding. Little is known about how higher-order chromatin packaging might affect gene expression. SATB1 is a cell-type specific nuclear protein that recruits chromatin-remodeling factors and regulates numerous genes during thymocyte differentiation.

SATB1 targets chromatin remodelling to regulate genes over long distances.

Eukaryotic chromosomes are organized inside the nucleus in such a way that only a subset of the genome is expressed in any given cell type, but the details of this organization are largely unknown. SATB1 ('special AT-rich sequence binding 1'), a protein found predominantly in thymocytes, regulates genes by folding chromatin into loop domains, tethering specialized DNA elements to an SATB1 network structure. Ablation of SATB1 by gene targeting results in temporal and spatial mis-expression of numerous genes and arrested T-cell development, suggesting that SATB1 is a cell-type specific global gene regulator.