USDA/ARS Children's Nutrition Research Center, Department of Pediatrics, Baylor College of Medicine, Houston, TX, USA.
J Mammary Gland Biol Neoplasia. 2010 Mar;15(1):85-100. doi: 10.1007/s10911-010-9170-4. Epub 2010 Feb 17.
Most of the development and functional differentiation in the mammary gland occur after birth. Epigenetics is defined as the stable alterations in gene expression potential that arise during development and proliferation. Epigenetic changes are mediated at the biochemical level by the chromatin conformation initiated by DNA methylation, histone variants, post-translational modifications of histones, non-histone chromatin proteins, and non-coding RNAs. Epigenetics plays a key role in development. However, very little is known about its role in the developing mammary gland or how it might integrate the many signalling pathways involved in mammary gland development and function that have been discovered during the past few decades. An inverse relationship between marks of closed (DNA methylation) or open chromatin (DnaseI hypersensitivity, certain histone modifications) and milk protein gene expression has been documented. Recent studies have shown that during development and functional differentiation, both global and local chromatin changes occur. Locally, chromatin at distal regulatory elements and promoters of milk protein genes gains a more open conformation. Furthermore, changes occur both in looping between regulatory elements and attachment to nuclear matrix. These changes are induced by developmental signals and environmental conditions. Additionally, distinct epigenetic patterns have been identified in mammary gland stem and progenitor cell sub-populations. Together, these findings suggest that epigenetics plays a role in mammary development and function. With the new tools for epigenomics developed in recent years, we now can begin to establish a framework for the role of epigenetics in mammary gland development and disease.
大多数乳腺的发育和功能分化发生在出生后。表观遗传学被定义为在发育和增殖过程中出现的基因表达潜力的稳定改变。表观遗传变化在生化水平上是由 DNA 甲基化、组蛋白变体、组蛋白的翻译后修饰、非组蛋白染色质蛋白和非编码 RNA 引发的染色质构象介导的。表观遗传学在发育中起着关键作用。然而，我们对其在发育中的乳腺中的作用知之甚少，也不知道它如何整合过去几十年中发现的参与乳腺发育和功能的许多信号通路。封闭（DNA 甲基化）或开放染色质（DnaseI 超敏反应、某些组蛋白修饰）标记与乳蛋白基因表达之间存在反比关系已被记录在案。最近的研究表明，在发育和功能分化过程中，都会发生全局和局部染色质变化。在局部，乳蛋白基因的远端调节元件和启动子处的染色质获得更开放的构象。此外，在调节元件之间的环化和与核基质的附着方面也会发生变化。这些变化是由发育信号和环境条件诱导的。此外，在乳腺干细胞和祖细胞亚群中已经鉴定出不同的表观遗传模式。总之，这些发现表明表观遗传学在乳腺发育和功能中发挥作用。随着近年来开发的表观基因组学新工具，我们现在可以开始建立一个框架，了解表观遗传学在乳腺发育和疾病中的作用。
