Transcription and chromatin regulation by TAF4b during cellular quiescence of developing prospermatogonia.
Transcription and chromatin regulation by TAF4b during cellular quiescence of developing prospermatogonia.
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DOI：
10.3389/fcell.2023.1270408
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发表时间：
2023
影响因子：
5.5
通讯作者：
Freiman, Richard N.
中科院分区：
文献类型：
--
作者：
Gura, Megan A.;Bartholomew, Myles A.;Abt, Kimberly M.;Relovska, Sona;Seymour, Kimberly A.;Freiman, Richard N.
关键词：
前精原细胞（Prospermatogonia，ProSpg）是连接雄性原始生殖细胞的胚胎发育和生后精原细胞和精原干细胞的健康建立的纽带。虽然这些生精前体细胞经历周期和静止的特征性转变，但这些发育标志背后的转录事件仍然未知。在这里，我们研究了TBP相关因子4b（Taf4b）的表达和功能，在静止的小鼠ProSpg的及时发展，使用整合的基因表达谱和染色质图谱。我们发现，Taf4b mRNA的表达升高，在有丝分裂到静止的ProSpg和Taf4b缺陷的ProSpg的过渡延迟进入静止。基因本体论、蛋白质网络分析和染色质图谱表明，TAF4b是ProSpg静止期染色质和细胞周期相关基因表达程序的直接和间接调节剂。通过增殖细胞核抗原（PCNA）的免疫染色，进一步验证了由于TAF4b的丢失而导致的这些细胞周期mRNA的变化。总之，这些数据表明，TAF4b是一个关键的转录调节染色质和静止状态的发展哺乳动物生精前体谱系。
Prospermatogonia (ProSpg) link the embryonic development of male primordial germ cells to the healthy establishment of postnatal spermatogonia and spermatogonial stem cells. While these spermatogenic precursor cells undergo the characteristic transitions of cycling and quiescence, the transcriptional events underlying these developmental hallmarks remain unknown. Here, we investigated the expression and function of TBP-associated factor 4b (Taf4b) in the timely development of quiescent mouse ProSpg using an integration of gene expression profiling and chromatin mapping. We find that Taf4b mRNA expression is elevated during the transition of mitotic-to-quiescent ProSpg and Taf4b-deficient ProSpg are delayed in their entry into quiescence. Gene ontology, protein network analysis, and chromatin mapping demonstrate that TAF4b is a direct and indirect regulator of chromatin and cell cycle-related gene expression programs during ProSpg quiescence. Further validation of these cell cycle mRNA changes due to the loss of TAF4b was accomplished via immunostaining for proliferating cell nuclear antigen (PCNA). Together, these data indicate that TAF4b is a key transcriptional regulator of the chromatin and quiescent state of the developing mammalian spermatogenic precursor lineage.
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影响因子：
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通讯作者：
Freiman, Richard N.
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通讯作者：
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