肝脏发育过程中转录因子的调控

肝脏的发育经历了一系列内胚层和中胚层之间复杂的相互作用,其中转录因子扮演着重要角色。肝脏发育主要可分为两个阶段,首先是前肠内胚层感受心脏中胚层的信号而建立响应态(competence),肝向特化基因逐渐表达并形成新生肝芽。此阶段受到转录调控网络的控制,其中FoxA家族,锌指结构转录因子GATA4/6,同源结构域因子Hhex、Onecut1、Onecut2和Prox1发挥了重要的作用。其次是肝脏内细胞群体如肝细胞和胆管细胞的分化成熟阶段。这个过程的完成主要受肝富集转录因子HNF1α、HNF4、HNF6和C/EBPα的调控。本文概述了肝脏发育中复杂的转录调控网络及其发挥的作用。     

Histone H2B subtypes are dispensable during the yeast cell cycle

Saccharomyces cerevisiae contains two histone H2B protein subtypes, H2B1 and H2B2, which differ at 4 of 130 amino acids. We describe experiments that test whether both histone H2B subtypes are required for the completion of any stage in the yeast life cycle. Frameshift mutations were introduced into cloned copies of the H2B1 and H2B2 genes. These altered genes were integrated into the yeast genome by transformation and replaced the wild-type genes through recombination. We thus obtained strains that lacked functional H2B1 or H2B2 proteins. These mutant strains survive as haploids and homozygous diploids. During vegetative growth, they divide at the same rate as wild-type cells and are able to mate, sporulate and germinate. The h2b1^? cells grew more slowly after germination than h2b2^? or wild-type spores, but otherwise the mutants were indistinguishable from each other or from wild-type cells. We also attempted to make a strain that was mutant in both genes for H2B. We examined spores derived from a diploid that is heterozygous for both histone mutations. The two genes assort independently, so we expect one in four spores to be h2b1^?h2b2^?. Of 61 spore colonies examined, none was mutant at both loci. Our results indicate that the double mutant can germinate and bud once but cannot grow further. Since the yeast life cycle can be completed in the absence of either but not both histone H2B subtypes, we conclude that neither protein has a unique essential function.