Related Experiment Video
Updated: Jul 15, 2026

In Vitro Biochemical Assays using Biotin Labels to Study Protein-Nucleic Acid Interactions
Published on: July 17, 2019
ALKBH5 is required to maintain proper SETDB1 protein levels associated with meiotic sex chromosome inactivation
Qingqing Chen1,2, Yu Xiang1,2, Yang Song1,2
1Key Laboratory of Reproductive Genetics (Ministry of Education), Women's Hospital, Zhejiang University School of Medicine, Hangzhou, China.
Abstract:
N6-methyladenosine (m6A) is the most abundant RNA modification in eukaryotes. ALKBH5 is an m6A demethylase that is essential for spermatogenesis. However, its function in meiotic prophase remains elusive. Here, we report that Alkbh5-knockout spermatocytes exhibit normal double-strand break (DSB) formation, homologous recombination and synapsis on autosomes but impaired synapsis between sex chromosomes. ALKBH5 depletion causes a significantly upregulated transcriptome on sex chromosomes and meiotic sex chromosome inactivation (MSCI) defects in spermatocytes at the pachytene stage. Mechanistically, ALKBH5 regulates SETDB1 expression in a post-transcriptional manner. Alkbh5 knockout inhibits SETDB1 protein expression, leading to the decreased SETDB1 signals on sex chromosomes and subsequently inhibiting H3K9me3 to form heterochromatin and silence transcriptional activity. Taken together, our findings identify ALKBH5 as a critical regulator of male meiosis by demonstrating that it is required to maintain proper SETDB1 protein levels, which in turn ensures the faithful execution of MSCI.
More Related Videos
Related Concept Videos
Meiosis II
The timing and cell division patterns of meiosis differ between males and females. In male meiosis, the centrosomes are part of the formation of the meiotic spindle. However, in oocytes, including that of humans, Drosophila,...
Meiosis II
Separation of Sister Chromatids
At the onset of anaphase, separase, a proteolytic enzyme, is...
Inhibition of Cdk Activity
Meiosis vs. Mitosis
Before the start of mitosis and meiosis I, the cell synthesizes DNA, resulting in two homologous copies of each chromosome. DNA synthesis is...
Dosage Compensation
In addition to sexual development, the X chromosome has genes involved in autosomal functions such as brain development and the immune system. Therefore, males and females with distinct numbers of X chromosomes will have...

