Department of Developmental Biochemistry, NYS Institute for Basic Research in Developmental Disabilities, 1050 Forest Hill Road, Staten Island, NY 10314, USA.
BMC Biochem. 2013 Jul 8;14:17. doi: 10.1186/1471-2091-14-17.
Hydroxysteroid (17beta) dehydrogenase X (HSD10) is a multifunctional protein encoded by the HSD17B10 gene at Xp11.2. In response to stress or hypoxia-ischemia its levels increase rapidly. Expression of this gene is also elevated significantly in colonic mucosa of the inactive ulcerative colitis patients. However, accurate information about its several transcripts is still lacking, and additional evidence for its escape from X-chromosome inactivation remains to be obtained in order to help settle a debate (He XY, Dobkin C, Yang SY: Does the HSD17B10 gene escape from X-inactivation? Eur J Hum Genet 2011, 19: 123-124).
Two major HSD17B10 transcription start sites were identified by primer extension at -37 and -6 as well as a minor start site at -12 nucleotides from the initiation codon ATG. Epigenetic analysis of the 5'-flanking region of the HSD17B10 gene showed that there was little 5-methylcytosine (< 3%) in a normal male, and that none of CpG dinucleotides in the CpG island approached 50% methylation in females.
The actual length of first exon of the HSD17B10 gene was found to be about a quarter larger than that originally reported. Its transcripts result from a slippery transcription complex. The hypomethylation of the CpG island provides additional evidence for the variable escape of the HSD17B10 gene from X-chromosome inactivation which could influence the range of severity of HSD10 deficiency, an inherited error in isoleucine metabolism, in heterozygous females.
羟甾体（17β）脱氢酶 X（HSD10）是一种多功能蛋白，由 Xp11.2 上的 HSD17B10 基因编码。在应激或缺氧缺血的情况下，其水平会迅速升高。该基因在非活动溃疡性结肠炎患者的结肠黏膜中的表达也显著升高。然而，关于其几个转录本的准确信息仍然缺乏，并且需要获得更多证据证明其逃避 X 染色体失活，以帮助解决争议（He XY、Dobkin C、Yang SY：HSD17B10 基因是否逃避 X 染色体失活？Eur J Hum Genet 2011, 19: 123-124）。
通过引物延伸在-37 和-6 处以及起始密码子 ATG 前 12 个核苷酸处鉴定了两个主要的 HSD17B10 转录起始位点。HSD17B10 基因 5'侧翼区的表观遗传分析表明，正常男性中 5-甲基胞嘧啶（<3%）很少，并且女性中 CpG 岛中的任何 CpG 二核苷酸都没有接近 50%的甲基化。
发现 HSD17B10 基因的第一外显子的实际长度比最初报道的要长四分之一左右。其转录物源自滑动转录复合物。CpG 岛的低甲基化为 HSD17B10 基因从 X 染色体失活中可变逃逸提供了额外证据，这可能影响 HSD10 缺乏症（异亮氨酸代谢的遗传性错误）杂合女性的严重程度范围。
