Publication Date:
2008-09-13
Description:
Homologous sets of transcription factors direct conserved tissue-specific gene expression, yet transcription factor-binding events diverge rapidly between closely related species. We used hepatocytes from an aneuploid mouse strain carrying human chromosome 21 to determine, on a chromosomal scale, whether interspecies differences in transcriptional regulation are primarily directed by human genetic sequence or mouse nuclear environment. Virtually all transcription factor-binding locations, landmarks of transcription initiation, and the resulting gene expression observed in human hepatocytes were recapitulated across the entire human chromosome 21 in the mouse hepatocyte nucleus. Thus, in homologous tissues, genetic sequence is largely responsible for directing transcriptional programs; interspecies differences in epigenetic machinery, cellular environment, and transcription factors themselves play secondary roles.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3717767/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉 〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3717767/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Wilson, Michael D -- Barbosa-Morais, Nuno L -- Schmidt, Dominic -- Conboy, Caitlin M -- Vanes, Lesley -- Tybulewicz, Victor L J -- Fisher, Elizabeth M C -- Tavare, Simon -- Odom, Duncan T -- 080174/Wellcome Trust/United Kingdom -- 15603/Cancer Research UK/United Kingdom -- 202218/European Research Council/International -- A15603/Cancer Research UK/United Kingdom -- G0601056/Medical Research Council/United Kingdom -- MC_U117527252/Medical Research Council/United Kingdom -- Medical Research Council/United Kingdom -- Wellcome Trust/United Kingdom -- New York, N.Y. -- Science. 2008 Oct 17;322(5900):434-8. doi: 10.1126/science.1160930. Epub 2008 Sep 11.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Cancer Research UK, Cambridge Research Institute, Li Ka Shing Centre, Robinson Way, Cambridge CB2 0RE, UK.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/18787134" target="_blank"〉PubMed〈/a〉
Keywords:
Animals
;
Base Sequence
;
Cell Nucleus/metabolism
;
Chromatin Assembly and Disassembly
;
Chromatin Immunoprecipitation
;
Chromosomes, Human, Pair 21/*genetics/metabolism
;
Disease Models, Animal
;
Down Syndrome/genetics
;
*Gene Expression Regulation
;
Hepatocyte Nuclear Factors/*metabolism
;
Hepatocytes/*metabolism
;
Histones/metabolism
;
Humans
;
Methylation
;
Mice
;
Oligonucleotide Array Sequence Analysis
;
*Regulatory Sequences, Nucleic Acid
;
Species Specificity
;
Transcription Initiation Site
;
*Transcription, Genetic
Print ISSN:
0036-8075
Electronic ISSN:
1095-9203
Topics:
Biology
,
Chemistry and Pharmacology
,
Computer Science
,
Medicine
,
Natural Sciences in General
,
Physics
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