Non-Canonical and Sexually Dimorphic X Dosage Compensation States in the Mouse and Human Germline.
Non-Canonical and Sexually Dimorphic X Dosage Compensation States in the Mouse and Human Germline.
复制标题
DOI：
10.1016/j.devcel.2016.12.023
复制
发表时间：
2017-02-06
影响因子：
11.8
通讯作者：
Turner JM
中科院分区：
文献类型：
--
作者：
Sangrithi MN;Royo H;Mahadevaiah SK;Ojarikre O;Bhaw L;Sesay A;Peters AH;Stadler M;Turner JM
体细胞X剂量补偿需要两种机制：X失活平衡男性（XY）和女性（XX）之间的X基因输出，而X上调，假设由Ohno和体内记录，平衡X基因与常染色体基因输出。X射线剂量补偿是否发生在生殖细胞中尚不清楚。我们发现，小鼠和人类生殖细胞表现出非典型的X剂量状态，不同的索马和性别之间。在全基因组重编程之前，存在X上调，与Ohno的假设一致。然而，随后，它被擦除。在女性中，擦除伴随着X失活的丧失，导致X剂量过量。相反，在男性中，擦除导致永久性X剂量失代偿。性染色体异常模型表现出“性别逆转”的X剂量状态：XX男性，像XX女性一样，出现X剂量过量，而XO女性，像XY男性一样，出现X剂量失代偿。因此，生殖系X剂量补偿状态是由X染色体数目决定的，而不是表型性别。生殖细胞和索马之间的X剂量补偿状态的这些意想不到的差异为性染色体不育提供了独特的视角。生殖细胞中的X剂量补偿在GWR期间重置PGCs在GWR之前表现出X上调，与Ohno的假设一致，在GWR期间X上调丢失小鼠和人类生殖细胞表现出性二态的X剂量状态。生殖细胞在减数分裂之前重置其表观基因组和转录组。Sangrithi等人表明生殖细胞中存在独特X染色体剂量补偿状态。这些状态是由存在的X染色体的数量而不是表型性别决定的，这为性染色体非整倍性相关的不育提供了不同的视角。
Somatic X dosage compensation requires two mechanisms: X inactivation balances X gene output between males (XY) and females (XX), while X upregulation, hypothesized by Ohno and documented in vivo, balances X gene with autosomal gene output. Whether X dosage compensation occurs in germ cells is unclear. We show that mouse and human germ cells exhibit non-canonical X dosage states that differ from the soma and between the sexes. Prior to genome-wide reprogramming, X upregulation is present, consistent with Ohno's hypothesis. Subsequently, however, it is erased. In females, erasure follows loss of X inactivation, causing X dosage excess. Conversely, in males, erasure leads to permanent X dosage decompensation. Sex chromosomally abnormal models exhibit a “sex-reversed” X dosage state: XX males, like XX females, develop X dosage excess, while XO females, like XY males, develop X dosage decompensation. Thus, germline X dosage compensation states are determined by X chromosome number, not phenotypic sex. These unexpected differences in X dosage compensation states between germline and soma offer unique perspectives on sex chromosome infertility. X dosage compensation in germ cells is reset during GWR PGCs exhibit X upregulation before GWR, in keeping with Ohno's hypothesis X upregulation is lost during GWR Mouse and human germ cells exhibit X dosage states that are sexually dimorphic Germ cells reset their epigenome and transcriptome prior to meiosis. Sangrithi et al. show that unique X chromosome dosage compensation states prevail in germ cells. These states are determined by the number of X chromosomes present rather than phenotypic sex, providing a different perspective on infertility associated with sex chromosome aneuploidy.