The role of the histone methyltransferase SET domain bifurcated 1 during palatal development

Sakurako Kano; Norihisa Higashihori; Phyo Thiha; Masaki Takechi; Sachiko Iseki; Keiji Moriyama

doi:10.1016/j.bbrc.2022.01.127

The role of the histone methyltransferase SET domain bifurcated 1 during palatal development

Biochem Biophys Res Commun. 2022 Apr 2:598:74-80. doi: 10.1016/j.bbrc.2022.01.127. Epub 2022 Feb 2.

Authors

Sakurako Kano¹, Norihisa Higashihori², Phyo Thiha¹, Masaki Takechi³, Sachiko Iseki⁴, Keiji Moriyama¹

Affiliations

¹ Maxillofacial Orthognathics, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo, 113-8549, Japan.
² Maxillofacial Orthognathics, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo, 113-8549, Japan. Electronic address: n-higashihori.mort@tmd.ac.jp.
³ Maxillofacial Anatomy, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo, 113-8549, Japan.
⁴ Molecular Craniofacial Embryology, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo, 113-8549, Japan.

PMID: 35151207
DOI: 10.1016/j.bbrc.2022.01.127

Abstract

The histone methyltransferase SET domain bifurcated 1 (SETDB1) catalyzes the trimethylation of lysine 9 of histone H3, thereby regulating gene expression. In this study, we used conditional knockout mice, where Setdb1 was deleted only in neural crest cells (Setdb1^fl/fl,^{Wnt1-Cre +} mice), to clarify the role of SETDB1 in palatal development. Setdb1^fl/fl,^{Wnt1-Cre +} mice died shortly after birth due to a cleft palate with full penetration. Reduced palatal mesenchyme proliferation was seen in Setdb1^fl/fl,^{Wnt1-Cre +} mice, which might be a possible mechanism of cleft palate development. Quantitative RT-PCR and in situ hybridization showed that expression of the Pax9, Bmp4, Bmpr1a, Wnt5a, and Fgf10 genes, known to be important for palatal development, were markedly decreased in the palatal mesenchyme of Setdb1^fl/fl,^{Wnt1-Cre +} mice. Along with these phenomena, SMAD1/5/9 phosphorylation was decreased by the loss of Setdb1. Our results demonstrated that SETDB1 is indispensable for palatal development partially through its proliferative effect. Taken together with previous reports that PAX9 regulates BMP signaling during palatal development which implies that loss of Setdb1 may be involved in the cleft palate development by decreasing SMAD-dependent BMP signaling through Pax9.

Keywords: Cleft palate; Epigenetic; PAX9; Proliferation; SETDB1; Wnt1-Cre.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Bone Morphogenetic Proteins / genetics
Bone Morphogenetic Proteins / metabolism
Cell Proliferation / genetics
Cleft Palate / genetics
Gene Expression Regulation, Developmental*
Histone-Lysine N-Methyltransferase / genetics
Histone-Lysine N-Methyltransferase / physiology*
Mice
Mice, Inbred C57BL
Mice, Knockout
Mice, Transgenic
Neural Crest / physiopathology
PAX9 Transcription Factor / genetics
PAX9 Transcription Factor / metabolism
Palate / abnormalities
Palate / embryology*
Palate / pathology
Smad Proteins / genetics
Smad Proteins / metabolism
Zebrafish Proteins / genetics
Zebrafish Proteins / metabolism

Substances

Bone Morphogenetic Proteins
PAX9 Transcription Factor
Smad Proteins
Zebrafish Proteins
pax9 protein, zebrafish
Histone-Lysine N-Methyltransferase
SETDB1 protein, mouse