Biology subjects

Nogami, J.

Publications and source records attributed to Nogami, J..

4 recordsLinked to original sources

bioRxiv2020

Tracking H3K27me3 and H4K20me1 dynamics during XCI reveals similarities in recruitment mechanism

During X chromosome inactivation (XCI), in female placental mammals, gene silencing is initiated by the Xist long-noncoding RNA. Xist accumulation at the X leads to enrichment of specific chromatin marks, including PRC2-dependent H3K27me3 and SETD8-dependent H4K20me1. However, the dynamics of this process in relation to Xist RNA accumulation remains unknown as is the molecular mechanism allowing for H4K20me1 enrichment. To follow XCI dynamics in living cells, we developed a genetically-encoded, H3K27me3-specific intracellular antibody, or H3K27me3-mintbody. By combining it with live-imaging of H4K20me1, the X chromosome and Xist RNA we uncover similarities in the initial accumulation dynamics of H3K27me3 and H4K20me1. Further ChIP-seq analysis confirmed concurrent accumulation of both marks during XCI albeit with distinct genomic distributions. Using a Xist B and C repeat mutant, which can silence the X but does not allow for H3K27me3 deposition, we also found a lack of H4K20me1 enrichment. Thus, these two marks accumulate at the X thanks to the same region of Xist and H4K20me1 in particular may have a role in the chromatin compaction that characterises facultative heterochromatin.

developmental biology↗

bioRxiv2020

Hoxa10 mediates positional memory to govern stem cell function in adult skeletal muscle

Skeletal muscle stem cells (satellite cells) are distributed throughout the body with heterogeneous properties that corresponds to region-specific pathophysiology. However, topographical genes that have functions remain unidentified in satellite cells of adult muscle. Here, we showed that expression of Homeobox (Hox)-A cluster genes, key regulators of the embryonic body plan, was robustly maintained in both muscles and satellite cells in adult mice and humans, which recapitulates their embryonic origin. We observed that regionally specific expressed Hox genes were linked to hypermethylation of the Hox-A locus. We examined Hoxa10 inactivation in satellite cells and found it led to genomic instability and mitotic catastrophe, which resulted in a decline in the regionally specific regenerative ability of muscles in adult mice. Thus, our results showed that Hox gene expression profiles instill the embryonic history in satellite cells as positional memory, potentially modulating the region-specificity in adult skeletal muscles.

developmental biology↗

bioRxiv2019

Calcineurin broadly regulates the initiation of skeletal muscle-specific gene expression by binding target promoters and facilitating the interaction of the SWI/SNF chromatin remodeling enzyme

Calcineurin (Cn) is a calcium-activated serine/threonine protein phosphatase that is broadly implicated in diverse cellular processes, including the regulation of gene expression. During skeletal muscle differentiation, Cn activates the NFAT transcription factor but also promotes differentiation by counteracting the negative influences of protein kinase C beta (PKC{beta}) via dephosphorylation and activation of BRG1, an enzymatic subunit of the mammalian SWI/SNF ATP-dependent chromatin remodeling enzyme. Here we identified four major temporal patterns of Cn-dependent gene expression in differentiating myoblasts and determined that Cn is broadly required for the activation of the myogenic gene expression program. Mechanistically, Cn promotes gene expression through direct binding to myogenic promoter sequences and facilitating the binding of BRG1, other SWI/SNF subunit proteins, and MyoD, a critical lineage determinant for skeletal muscle differentiation. We conclude that the Cn phosphatase directly impacts the expression of myogenic genes by promoting ATP-dependent chromatin remodeling and formation of transcription-competent promoters.

molecular biology↗

bioRxiv2018

Cell competition corrects noisy Wnt morphogen gradients to achieve robust patterning

Morphogen signaling forms an activity gradient and instructs cell identities in a signaling strength-dependent manner to pattern developing tissues. However, developing tissues also undergo dynamic morphogenesis, which may produce cells with unfit morphogen signaling and consequent noisy morphogen gradient. Here we show that a cell competition-related system corrects such noisy morphogen gradients. Zebrafish imaging analyses of the Wnt/{beta}-catenin signaling-gradient, which acts as a morphogen to establish embryonic anterior-posterior patterning, revealed that unfit cells with abnormal Wnt/{beta}-catenin activity spontaneously appear and produce noise in the Wnt/{beta}-catenin-gradient. Communication between the unfit and neighboring fit cells via cadherin proteins stimulates the apoptosis of the unfit cells by activating Smad signaling and reactive oxygen species production. This unfit cell elimination is required for proper Wnt/{beta}-catenin-gradient formation and consequent anterior-posterior patterning. Because this gradient controls patterning not only in the embryo but also in adult tissues, this system may support tissue robustness and disease prevention.

cell biology↗