Species-specific transcription in mice carrying human chromosome 21.

Journal article

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.

Authors: Wilson, MD; Barbosa-Morais, N; Schmidt, D; Conboy, C; Vanes, L

• Journal: Science (New York, N.Y.)
• Volume: 322
• Issue: 5900
• Pages: 434-438
• Publication date: 2008-10-01
• DOI: 10.1126/science.1160930
• EISSN: 1095-9203
• ISSN: 0036-8075
• Language: English
• Keywords: Base Sequence; Disease Models, Animal; Regulatory Sequences, Nucleic Acid; Mice; Oligonucleotide Array Sequence Analysis; Hepatocyte Nuclear Factors; Cell Nucleus; Species Specificity; Down Syndrome; Chromatin Assembly and Disassembly; Transcription, Genetic; Chromosomes, Human, Pair 21; Methylation; Animals; Gene Expression Regulation; Hepatocytes; Transcription Initiation Site; Humans; Histones; Chromatin Immunoprecipitation