SCML2

Last update 08 May 2025

Basic Info

Synonyms

Scm polycomb group protein like 2, SCML2, Sex comb on midleg-like protein 2

Introduction

Putative Polycomb group (PcG) protein. PcG proteins act by forming multiprotein complexes, which are required to maintain the transcriptionally repressive state of homeotic genes throughout development (By similarity).

100 Clinical Results associated with SCML2

100 Translational Medicine associated with SCML2

0 Patents (Medical) associated with SCML2

Literatures (Medical) associated with SCML2

01 Jan 2025·Advanced Science

METTL16 is Required for Meiotic Sex Chromosome Inactivation and DSB Formation and Recombination during Male Meiosis

Article

Author: Gao, Huihui ; Yang, Shiyu ; Wang, Xiaoli ; Zhang, Yuting ; Gui, Yiqian ; Xiong, Mengneng ; Zhang, Jin ; Yuan, Shuiqiao ; Xiong, Wenjing ; Yin, Lisha ; Jiang, Nan ; Li, Tao ; Li, Yi ; Wang, Fengli ; Zhang, Youzhi ; Xiong, Xinxin ; Liu, Kuan

AbstractMeiosis in males is a critical process that ensures complete spermatogenesis and genetic diversity. However, the key regulators involved in this process and the underlying molecular mechanisms remain unclear. Here, we report an essential role of the m6A methyltransferase METTL16 in meiotic sex chromosome inactivation (MSCI), double‐strand break (DSB) formation, homologous recombination and SYCP1 deposition during male meiosis. METTL16 depletion results in a significantly upregulated transcriptome on sex chromosomes in pachytene spermatocytes and leads to reduced DSB formation and recombination, and increased SYCP1 depositioin during the first wave of spermatogenesis. Mechanistically, in pachytene spermatocytes, METTL16 interacts with MDC1/SCML2 to coordinate DNA damage response (DDR) and XY body epigenetic modifications that establish and maintain MSCI, and in early meiotic prophase I, METTL16 regulates DSB formation and recombination by regulating protein levels of meiosis‐related genes. Furthermore, multi‐omics analyses reveal that METTL16 interacts with translational factors and controls m6A levels in the RNAs of meiosis‐related genes (e.g., Ubr2) to regulate the expression of critical meiotic regulators. Collectively, this study identified METTL16 as a key regulator of male meiosis and demonstrated that it modulates meiosis by interacting with MSCI‐related factors and regulating m6A levels and translational efficiency (TE) of meiosis‐related genes.

01 Oct 2023·iScience

Discordant interactions between YAP1 and polycomb group protein SCML2 determine cell fate

Article

Author: Cinar, Bekir ; Zhang, Qiang ; Dwead, Abdulrahman M ; Zou, Jin ; Wang, Guangdi ; Boston, Ava M ; Khazaw, Kezhan ; Al-Mathkour, Marwah M

The Polycomb group protein SCML2 and the transcriptional cofactor YAP1 regulate diverse cellular biology, including stem cell maintenance, developmental processes, and gene regulation in mammals and flies. However, their molecular and functional interactions are unknown. Here, we show that SCML2 interacts with YAP1, as revealed by immunological assays and mass spectroscopy. We have demonstrated that the steroid hormone androgen regulates the interaction of SCML2 with YAP1 in human tumor cell models. Our proximity ligation assay and GST pulldown showed that SCML2 and YAP1 physically interacted with each other. Silencing SCML2 by RNAi changed the growth behaviors of cells in response to androgen signaling. Mechanistically, this phenomenon is attributed to the interplay between distinct chromatin modifications and transcriptional programs, likely coordinated by the opposing SCML2 and YAP1 activity. These findings suggest that YAP1 and SCML2 cooperate to regulate cell growth, cell survival, and tumor biology downstream of steroid hormones.

21 Jul 2023·Nucleic acids research

Polycomb protein SCML2 mediates paternal epigenetic inheritance through sperm chromatin.

Article

Author: Maezawa, So ; Sakashita, Akihiko ; Wakayama, Teruhiko ; Ooga, Masatoshi ; Wakayama, Sayaka ; Namekawa, Satoshi H ; Takeuchi, Chikara ; Otsuka, Kai

Sperm chromatin retains small amounts of histones, and chromatin states of sperm mirror gene expression programs of the next generation. However, it remains largely unknown how paternal epigenetic information is transmitted through sperm chromatin. Here, we present a novel mouse model of paternal epigenetic inheritance, in which deposition of Polycomb repressive complex 2 (PRC2) mediated-repressive H3K27me3 is attenuated in the paternal germline. By applying modified methods of assisted reproductive technology using testicular sperm, we rescued infertility of mice missing Polycomb protein SCML2, which regulates germline gene expression by establishing H3K27me3 on bivalent promoters with other active marks H3K4me2/3. We profiled epigenomic states (H3K27me3 and H3K4me3) of testicular sperm and epididymal sperm, demonstrating that the epididymal pattern of the sperm epigenome is already established in testicular sperm and that SCML2 is required for this process. In F1 males of X-linked Scml2-knockout mice, which have a wild-type genotype, gene expression is dysregulated in the male germline during spermiogenesis. These dysregulated genes are targets of SCML2-mediated H3K27me3 in F0 sperm. Further, dysregulation of gene expression was observed in the mutant-derived wild-type F1 preimplantation embryos. Together, we present functional evidence that the classic epigenetic regulator Polycomb mediates paternal epigenetic inheritance through sperm chromatin.

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SCML2

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