HMGN2 represses gene transcription via interaction with transcription factors Lef-1 and Pitx2 during amelogenesis

Eliason, Steven; Su, Dan; Pinho, Flavia Oliveira; Sun, Zhao; Zhang, Zichao; Li, Xiao; Sweat, Mason; Venugopalan, Shankar Rengasamy; He, Bing; Bustin, Michael; Amendt, Brad A.

doi:10.1016/j.jbc.2022.102295

Cited by 5 publications

(2 citation statements)

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“…HMGN proteins have been shown to affect the rate of cell fate conversions in several biological systems (Furusawa et al 2006; Zhang et al 2016; Deng et al 2017; He et al 2018). Most likely, HMGNs modulate cellular differentiation by preferentially binding to nucleosomes containing histone marks of active chromatin such as H3K27ac and H3K4me3, thereby modulating the binding of transcription factors to regulatory chromatin (Amen et al 2008; Eliason et al 2022; Zhang et al 2022). We postulate that the presence of HMGN at cell type–specific regulatory chromatin sites stabilizes the cell identity (He et al 2018; Garza-Manero et al 2019).…”

Section: Discussionmentioning

confidence: 99%

“…Transcription factor AmeloD regulates early stage ameloblast migration, while transcription factor epiprofin regulates ameloblast terminal differentiation and transcription activation (Nakamura et al 2008; Chiba et al 2019; Miao et al 2022). Additional transcription factors, including PITX2, LEF1, DLX3, and CIP2/BCL11b, also play significant roles during ameloblast differentiation (Amen et al 2008; Golonzhka et al 2009; Li et al 2014; Duverger et al 2017; Eliason et al 2022). These studies greatly enhanced our knowledge of amelogenesis, yet the regulatory mechanisms that establish ameloblast-specific cell identity are still not fully understood.…”

Section: Introductionmentioning

confidence: 99%

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Epigenetic Regulation of Ameloblast Differentiation by HMGN Proteins

He,

Kram,

Furusawa

et al. 2023

J Dent Res

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Dental enamel formation is coordinated by ameloblast differentiation, production of enamel matrix proteins, and crystal growth. The factors regulating ameloblast differentiation are not fully understood. Here we show that the high mobility group N (HMGN) nucleosomal binding proteins modulate the rate of ameloblast differentiation and enamel formation. We found that HMGN1 and HMGN2 proteins are downregulated during mouse ameloblast differentiation. Genetically altered mice lacking HMGN1 and HMGN2 proteins show faster ameloblast differentiation and a higher rate of enamel deposition in mice molars and incisors. In vitro differentiation of induced pluripotent stem cells to dental epithelium cells showed that HMGN proteins modulate the expression and chromatin accessibility of ameloblast-specific genes and affect the binding of transcription factors epiprofin and PITX2 to ameloblast-specific genes. Our results suggest that HMGN proteins regulate ameloblast differentiation and enamel mineralization by modulating lineage-specific chromatin accessibility and transcription factor binding to ameloblast regulatory sites.

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