Passage
The sex chromosomes X and Y are involved in mammalian sex determination. Organisms with two wild-type (WT) X chromosomes develop as females (XX) , but those with a combination of WT X and Y chromosomes develop as males (XY) (Table 1) . Both sexes also inherit a set of autosomes (nonsex chromosomes) . Humans inherit 22 pairs of autosomes (44 total) . In contrast, rabbits inherit 21 pairs of autosomes (42 total) .Table 1 Chromosome Types Inherited by a Male and Female Rabbit (Note: The Y chromosome has fewer alleles than the X chromosome.)
Specifically, the SRY gene, located on the mammalian Y chromosome, is crucial for male sex determination and induction of testis development. Studies in mammals have shown that regardless of an organism's combination of sex chromosomes, fetuses will always develop as female in the absence of the SRY protein. In addition, one of the X chromosomes becomes inactivated in WT,XX females to prevent them from having double the amount of X-chromosome gene products as WT,XY males.Sp1 is a transcription factor with demonstrated regulatory control of SRY gene expression, and XY individuals with mutations affecting the Sp1 binding site on the SRY gene have been shown to develop female sex characteristics. Unlike SRY, the gene for Sp1 is located on an autosome.Researchers knocked out (KO) Sp1 binding sites on the SRY gene in rabbit embryos (Sp1 KO,XY rabbits) and observed their sexual development following implantation in surrogate mothers. The relationship between the SRY gene and sexual development can be explained by the following experimental observations: Most Sp1 KO,XY rabbits had female genitalia and displayed normal mating behaviors.
Sp1 KO,XY rabbits had significantly smaller ovaries and fewer follicles than WT,XX rabbits.
No significant differences were observed in the cervix and uterus between Sp1 KO,XY and WT,XX rabbits.
There was significantly reduced SRY expression in Sp1 KO,XY rabbits when compared to WT,XY males.
WT,XY male rabbits had significantly higher testosterone levels when compared to Sp1 KO,XY rabbits.
Sp1 KO,XY rabbits were infertile when mated with WT,XY males.
Sp1 KO,XY rabbits could become pregnant via embryo transfer.
Song Y et al. Mutation of the Sp1 binding site in the 5' flanking region of SRY causes sex reversal in rabbits. Oncotarget. 2017; 8(24) :38176-83.
-A gene expression assay shows that the SRY gene is expressed in male embryos during the early stages of development. Which of the following best describes the DNA methylation pattern exhibited by the SRY gene in embryonic gonadal cells compared to embryonic cardiac cells?

Question

Passage
The sex chromosomes X and Y are involved in mammalian sex determination. Organisms with two wild-type (WT) X chromosomes develop as females (XX) , but those with a combination of WT X and Y chromosomes develop as males (XY) (Table 1) . Both sexes also inherit a set of autosomes (nonsex chromosomes) . Humans inherit 22 pairs of autosomes (44 total) . In contrast, rabbits inherit 21 pairs of autosomes (42 total) .Table 1 Chromosome Types Inherited by a Male and Female Rabbit (Note: The Y chromosome has fewer alleles than the X chromosome.)

Specifically, the SRY gene, located on the mammalian Y chromosome, is crucial for male sex determination and induction of testis development. Studies in mammals have shown that regardless of an organism's combination of sex chromosomes, fetuses will always develop as female in the absence of the SRY protein. In addition, one of the X chromosomes becomes inactivated in WT,XX females to prevent them from having double the amount of X-chromosome gene products as WT,XY males.Sp1 is a transcription factor with demonstrated regulatory control of SRY gene expression, and XY individuals with mutations affecting the Sp1 binding site on the SRY gene have been shown to develop female sex characteristics. Unlike SRY, the gene for Sp1 is located on an autosome.Researchers knocked out (KO) Sp1 binding sites on the SRY gene in rabbit embryos (Sp1 KO,XY rabbits) and observed their sexual development following implantation in surrogate mothers. The relationship between the SRY gene and sexual development can be explained by the following experimental observations: Most Sp1 KO,XY rabbits had female genitalia and displayed normal mating behaviors.
Sp1 KO,XY rabbits had significantly smaller ovaries and fewer follicles than WT,XX rabbits.
No significant differences were observed in the cervix and uterus between Sp1 KO,XY and WT,XX rabbits.
There was significantly reduced SRY expression in Sp1 KO,XY rabbits when compared to WT,XY males.
WT,XY male rabbits had significantly higher testosterone levels when compared to Sp1 KO,XY rabbits.
Sp1 KO,XY rabbits were infertile when mated with WT,XY males.
Sp1 KO,XY rabbits could become pregnant via embryo transfer.
Song Y et al. Mutation of the Sp1 binding site in the 5' flanking region of SRY causes sex reversal in rabbits. Oncotarget. 2017; 8(24) :38176-83.
-A gene expression assay shows that the SRY gene is expressed in male embryos during the early stages of development. Which of the following best describes the DNA methylation pattern exhibited by the SRY gene in embryonic gonadal cells compared to embryonic cardiac cells?

Quizplus · Accepted Answer

11ecba2d_100b_1888_a3bf_3705fd616a46_MD0008_00 All cells that comprise a multicellular organism contain identical genomes. These cells can differentiate (ie, specialize in structure and function) during development through differential regulation of gene expression. Chromatin structure (heterochromatin or euchromatin) affects gene expression by regulating transcription. Heterochromatin is tightly wound DNA characterized by low levels of histone acetylation and high levels of DNA methylation. Genes in these regions are considered silenced because the DNA is so tightly packed that it is inaccessible to the transcription machinery. In contrast, euchromatin is marked by high levels of histone acetylation and low levels of DNA methylation. This makes euchromatin looser and the DNA more accessible to the transcription machinery, allowing gene expression. In male embryos, gonadal cells develop into the testes (the site of spermatogenesis) whereas cardiac cells develop into heart tissue. Based on the passage, the SRY gene is crucial for male sex determination, meaning it is most likely highly expressed in cells important to male sexual development (gonadal cells). In contrast, cardiac cells do not play a role in male sexual development. Consequently, the SRY gene in gonadal cells will likely exhibit higher expression than the SRY gene in cardiac cells and exist in the form of euchromatin (ie, with lower levels of DNA methylation and higher levels of histone acetylation). (Choice A) In the male embryo, gonadal cells express SRY but cardiac cells do not. Accordingly, the SRY gene region in gonadal cells must be accessible to the transcription machinery, and therefore exhibits lower levels of DNA methylation compared to cardiac cells. (Choice C) If the genomic region containing the SRY gene had similar levels of DNA methylation in both cell types, this would indicate that levels of SRY gene expression are similar in both cells. However, because gonadal cells (not cardiac cells) are involved in male sexual development, SRY gene methylation and expression would be expected to differ in the two cell types. (Choice D) All cells that comprise a multicellular organism contain the same DNA (ie, genome). Therefore, the SRY gene is present in all cells, and this comparison can be made. Educational objective: Heterochromatin is tightly packed DNA that is inaccessible to transcriptional machinery, preventing gene expression. Euchromatin is loosely packed DNA that is accessible to transcriptional machinery, allowing gene expression.

Passage The Sex Chromosomes X and Y Are Involved in Mammalian