Exploring cellular memory molecules marking competent and active transcriptions

Li Xin,Xue-Song Wu,Wei Song,Chih-Chuan Liang,De-Long Hao,Gong-Hong Wei,Xiang Lv,De-Pei Liu,Guo-Ling Zhou

doi:10.1186/1471-2199-8-31

Abstract

BackgroundDevelopment in higher eukaryotes involves programmed gene expression. Cell type-specific gene expression is established during this process and is inherited in succeeding cell cycles. Higher eukaryotes have evolved elegant mechanisms by which committed gene-expression states are transmitted through numerous cell divisions. Previous studies have shown that both DNase I-sensitive sites and the basal transcription factor TFIID remain on silenced mitotic chromosomes, suggesting that certain trans-factors might act as bookmarks, maintaining the information and transmitting it to the next generation.ResultsWe used the mouse globin gene clusters as a model system to examine the retention of active information on M-phase chromosomes and its contribution to the persistence of transcriptional competence of these gene clusters in murine erythroleukemia cells. In cells arrested in mitosis, the erythroid-specific activator NF-E2p45 remained associated with its binding sites on the globin gene loci, while the other major erythroid factor, GATA-1, was removed from chromosome. Moreover, despite mitotic chromatin condensation, the distant regulatory regions and promoters of transcriptionally competent globin gene loci are marked by a preserved histone code consisting in active histone modifications such as H3 acetylation, H3-K4 dimethylation and K79 dimethylation. Further analysis showed that other active genes are also locally marked by the preserved active histone code throughout mitotic inactivation of transcription.ConclusionOur results imply that certain kinds of specific protein factors and active histone modifications function as cellular memory markers for both competent and active genes during mitosis, and serve as a reactivated core for the resumption of transcription when the cells exit mitosis.

Highlights

Development in higher eukaryotes involves programmed gene expression
Erythroid-specific activator NF-E2, but not GATA-1, marking transcriptional competence of globin genes in murine erythroleukemia (MEL) cell during mitosis In MEL cells, DNase I sensitivity and hypersensitivity have been established on globin gene loci [14], suggesting that they have obtained potential transcription activity
There are some specific binding sites of erythroid-specific activators, such as GATA-1, NF-E2 and Fog-1, on globin gene clusters [15], whose occupancies largely contribute to the activation of globin genes

Summary

Introduction

Development in higher eukaryotes involves programmed gene expression. Cell type-specific gene expression is established during this process and is inherited in succeeding cell cycles. Previous studies have shown that both DNase I-sensitive sites and the basal transcription factor TFIID remain on silenced mitotic chromosomes, suggesting that certain trans-factors might act as bookmarks, maintaining the information and transmitting it to the generation. Previous studies have shown that DNase I-sensitive sites mark active genes on silenced mitotic chromosomes [2,3] This implies that certain factors withstand chromatin condensation and survive during mitosis to facilitate the rapid reactivation of genes in cell cycle. We found that the p45 subunit of the erythroid-specific activator NF-E2 is partially retained on its specific binding sites during mitosis, but another activator, GATA1, is not This suggests that NF-E2 can function as a 'bookmark' to maintain the active competence of the local chromatin domain during cell division

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Results

Discussion

Conclusion