Department of Biological Sciences, Konkuk University, 120 Neungdong-ro, Gwangjin-gu, Seoul, 05029, Republic of Korea.
Department of Biomedical Science and Engineering, Konkuk University, 120 Neungdong-ro, Gwangjin-gu, Seoul, 05029, Republic of Korea.
Biochem Biophys Res Commun. 2024 Dec 3;736:150863. doi: 10.1016/j.bbrc.2024.150863. Epub 2024 Oct 20.
The nuclear receptor-binding SET domain protein (NSD) gene family encodes histone methyltransferases that mono- and di-methylate lysine 36 on histone H3 (H3K36). Here, we examine the effects of NSD loss-of-function on transcription and heterochromatin formation in Drosophila to elucidate the role of NSD in chromatin structure regulation. Transcriptome analysis showed that NSD deletion activated more genes on chromosome 4, predominantly heterochromatic, than on other chromosomes. We further analyzed the position-effect variegation of fly eyes due to mini-white (mw) transgenes inserted at various chromosomal loci and found that NSD deletion promoted mw transgene expression on chromosome 4. Additionally, NSD deletion reduced the binding of heterochromatin markers HP1a and H3K9 to chromosome 4. These findings suggest that NSD deletion disrupts chromosome 4 heterochromatin structure by reducing HP1a binding, implying NSD's role as an epigenetic regulator of chromosome 4 silencing.
核受体结合 SET 域蛋白 (NSD) 基因家族编码组蛋白甲基转移酶，可单甲基化和二甲基化组蛋白 H3 上的赖氨酸 36 (H3K36)。在这里，我们研究了 NSD 功能丧失对果蝇转录和异染色质形成的影响，以阐明 NSD 在染色质结构调节中的作用。转录组分析表明，与其他染色体相比，NSD 缺失激活了更多位于 4 号染色体上的基因，主要是异染色质基因。我们进一步分析了由于插入各种染色体位置的 mini-white (mw) 转座子而导致的果蝇眼睛位置效应变异，并发现 NSD 缺失促进了 4 号染色体上 mw 转座子的表达。此外，NSD 缺失减少了异染色质标记物 HP1a 和 H3K9 与 4 号染色体的结合。这些发现表明，NSD 缺失通过减少 HP1a 结合破坏了 4 号染色体异染色质结构，暗示 NSD 作为 4 号染色体沉默的表观遗传调节剂的作用。
