Mammal-Specific Protein Associates with Male Chromatin, Required for Male Meiosis

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A new paper available today in PLoS Genetics suggests that a mammal-specific protein (DMRT7) related to the invertebrate sexual regulators Doublesex and MAB-3 controls the transition from meiotic sex chromosome inactivation to postmeiotic sex chromatin in males (1).

Genes related to the sexual regulator Doublesex of Drosophila have been found to control sexual development in a wide variety of animals, ranging from roundworms to mammals. In this paper, we investigate the function of the Dmrt7 gene, one of seven related genes in the mouse. Female mammals are XX and males are XY, a chromosomal difference that presents specific challenges during the meiotic phase of male germ cell development. Some of these are thought to be overcome by incorporating the X and Y chromo- somes into a specialized structure called the XY body. We find that DMRT7 protein is present in germ cells, localizes to the male XY body during meiosis, and is essential for male but not female fertility. The XY body normally is altered by recruitment of additional proteins and by specific modifications to histone proteins between the pachytene and diplotene stages of meiosis, but modification of the “sex chromatin” in Dmrt7 mutant cells is abnormal during this period. Because Dmrt7 is found in all branches of mammals, but not in other vertebrates, these results may indicate some commonality in regulation of sex chromatin among the mammals.


1. Kim S, Namekawa SH, Niswander LM, Ward JO, Lee JT, Bardwell VJ, Zarkower D. 2007. A mammal-specific Doublesex homolog associates with male sex chromatin and is required for male meiosis. PLoS Genetics 3(4): e62.

Gadd45a Promotes Epigenetic Gene Activation by Repair-Mediated DNA Demethylation

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Nature has published a letter from researchers at the German Cancer Research Center involving their implication of the gene Gadd45a in one of the black boxes of epigenetic mechanisms: demethylation.

DNA methylation is an epigenetic modification that is essential for gene silencing and genome stability in many organisms. Although methyltransferases that promote DNA methylation are well characterized, the molecular mechanism underlying active DNA demethylation is poorly understood and controversial. Here we show that Gadd45a (growth arrest and DNA-damage-inducible protein 45 alpha), a nuclear protein involved in maintenance of genomic stability, DNA repair and suppression of cell growth, has a key role in active DNA demethylation. Gadd45a overexpression activates methylation-silenced reporter plasmids and promotes global DNA demethylation. Gadd45a knockdown silences gene expression and leads to DNA hypermethylation. During active demethylation of oct4 in Xenopus laevis oocytes, Gadd45a is specifically recruited to the site of demethylation. Active demethylation occurs by DNA repair and Gadd45a interacts with and requires the DNA repair endonuclease XPG. We conclude that Gadd45a relieves epigenetic gene silencing by promoting DNA repair, which erases methylation marks.


One of the experiments from this paper seem to support the recent finding that demethylation of the proximal-promoter region is required for active transcription.

ScienceDaily offers a summary of this research adapted from a press release from the German Cancer Research Center. Link