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转录频率与细胞决定

Transcriptional frequency and cell determination.

作者信息

Flickinger R A

机构信息

Department of Biological Sciences, State University of New York at Buffalo, Buffalo, NY 14260, USA.

出版信息

J Theor Biol. 2005 Jan 21;232(2):151-6. doi: 10.1016/j.jtbi.2004.05.020.

Abstract

The relative base composition of DNA regulatory sequences of certain genes of undetermined multipotent progenitor cells may account for the frequency of transcription of these genes in cell determination. The sequences of these regulatory regions of cell determination genes that are more AT-rich would create the potential for transcription at a higher frequency due to their lower melting temperature, as well as propensity to bend. An increase of one or more of the high mobility group (HMG) chromatin proteins would preferentially bind the more AT-rich regulatory sequences, thereby increasing the rate of transcription. The amount of unphosphorylated H1 histone reacting with these same regulatory sites may decrease transcription frequency. The level of cell growth, i.e. total protein synthesis of a cell, is correlated positively with the synthesis of HMG proteins. H1 histone synthesis is linked to DNA replication. Unbalanced growth would alter the amounts of HMG proteins and H1 histone, thus changing transcriptional frequency. The greater the enrichment of AT sequences in the regulatory regions of the cell determination genes, the greater may be the extent of evolutionary conservation. Higher frequency of transcription of the cell determination genes with the more AT-rich regulatory sequences could account for the earlier expression of the more conserved cell determination genes during embryonic development. Preferential binding of H1 histone to the more AT-rich regulatory sequences would subsequently restrict their transcription before that of less conserved cell determination genes.

摘要

未分化多能祖细胞某些基因的DNA调控序列的相对碱基组成,可能解释了这些基因在细胞分化过程中的转录频率。细胞分化基因这些调控区域中富含AT的序列,由于其较低的解链温度以及弯曲倾向,会产生更高频率转录的可能性。一种或多种高迁移率族(HMG)染色质蛋白的增加,会优先结合富含AT的调控序列,从而提高转录速率。与这些相同调控位点反应的未磷酸化H1组蛋白的量,可能会降低转录频率。细胞生长水平,即细胞的总蛋白合成,与HMG蛋白的合成呈正相关。H1组蛋白的合成与DNA复制相关。生长不平衡会改变HMG蛋白和H1组蛋白的量,从而改变转录频率。细胞分化基因调控区域中AT序列的富集程度越高,进化保守程度可能就越高。具有更多富含AT调控序列的细胞分化基因的更高转录频率,可能解释了在胚胎发育过程中更保守的细胞分化基因更早表达的现象。H1组蛋白优先结合富含AT的调控序列,随后会在不太保守的细胞分化基因转录之前限制它们的转录。

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