Developmental role of HMGN proteins in Xenopus laevis

Abstract

HMGN proteins are architectural chromatin proteins that reduce the compaction of the chromatin fiber, facilitate access to nucleosomes and modulate replication and transcription processes. Here we demonstrate that in Xenopus laevis, the expression and cellular location of the HMGN proteins are developmentally regulated and that their misexpression leads to gross developmental defects in post-blastula embryos. HMGN transcripts and proteins are present throughout oogenesis; however, the proteins stored in the cytoplasm are not associated with lampbrush chromosomes, and are rapidly degraded when oocytes mature into eggs. During embryogenesis, HMGN expression is first detected in blastula stages and progresses to a tissue-specific expression reaching relative high levels in the mesodermal and neuroectodermal regions of tadpoles. Only after midblastula transition (MBT), alterations in the HMGN levels by either microinjection of recombinant proteins or by morpholino-antisense oligo treatments produced embryos with imperfectly closed blastopore, distorted body axis and showed abnormal head structures. Analyses of animal cap explants indicated that HMGN proteins are involved in the regulation of mesoderm specific genes. In addition, HMGN misexpression caused altered expression of specific genes at MBT rather than global changes of transcription rates. Our results demonstrate that proper embryonic development of Xenopus laevis requires precisely regulated levels of HMGN proteins and suggest that these nucleosomal binding proteins modulate the expression of specific genes.

Network of Dynamic Interactions between Histone H1 and High-Mobility-Group Proteins in Chromatin

“…The average nucleus contains 10 7 nucleosomes, an equal number of H1 molecules (59), and approximately 10 6 HMGB, 10 5 HMGN, and 10 4 HMGA molecules (12,31). While the amount of H1 varies little among cells, the cellular amounts of the various HMG proteins fluctuate significantly, especially during development (14,19,25,33,35). Certain malignancies are associated with significant increases in the levels of HMGA2 (22,23,49).…”

Downregulation of the nucleosome-binding protein 1 (NSBP1) gene can inhibit the in vitro and in vivo proliferation of prostate cancer cells

“…HMGN proteins are found only in vertebrates, and detailed developmental studies on HMGN expression patterns in Xenopus and in mice show that the expression level of HMGN proteins is tightly linked to differentiation [13,14]. During mouse embryogenesis, these HMGN genes are progressively downregulated throughout the entire embryo except in committed but continuously renewing cell types undergoing active differentiation, such as the basal layer of the epithelium or in kidney cells undergoing mesenchyme to epithelium transition [14][15][16].…”

Down-Regulation of Nucleosomal Binding Protein HMGN1 Expression during Embryogenesis Modulates Sox9 Expression in Chondrocytes

“…HMGNs modulate the levels of posttranslational modifications in the histone tails (17), most likely because their presence on nucleosomes affects the ability of nucleosome remodeling complexes to reach their targets. These findings and additional studies suggest that HMGN proteins modulate chromatin-related activities, including transcription (4).The expression level of Hmgn genes is related to cellular differentiation processes, such as erythropoiesis, myogenesis, osteoblast differentiation, kidney organogenesis, preimplantation development of early mouse embryo, and Xenopus embryogenesis (1,9,15,16,20,23,27). Transient depletion of HMGN proteins from one-or two-cell mouse embryos slowed the progression of preimplantation development (20).…”