chromatin organization in sperm may be the major functional consequence of base composition variation in the human genome精子染色质组织可能是主要功能后果人类基因组的碱基组成变化.pdfVIP

Chromatin Organization in Sperm May Be the Major Functional Consequence of Base Composition Variation in the Human Genome Tanya Vavouri1¤, Ben Lehner1,2* ´ 1 EMBL-CRG Systems Biology Unit, Centre for Genomic Regulation, Universitat Pompeu Fabra, Barcelona, Spain, 2 Institucio Catalana de Recerca i Estudis Avanc¸ats (ICREA), Centre for Genomic Regulation, Universitat Pompeu Fabra, Barcelona, Spain Abstract Chromatin in sperm is different from that in other cells, with most of the genome packaged by protamines not nucleosomes. Nucleosomes are, however, retained at some genomic sites, where they have the potential to transmit paternal epigenetic information. It is not understood how this retention is specified. Here we show that base composition is the major determinant of nucleosome retention in human sperm, predicting retention very well in both genic and non- genic regions of the genome. The retention of nucleosomes at GC-rich sequences with high intrinsic nucleosome affinity accounts for the previously reported retention at transcription start sites and at genes that regulate development. It also means that nucleosomes are retained at the start sites of most housekeeping genes. We also report a striking link between the retention of nucleosomes in sperm and the establishment of DNA methylation-free regions in the early embryo. Taken together, this suggests that paternal nucleosome transmission may facilitate robust gene regulation in the early embryo. We propose that chromatin organization in the male germline, rather than in somatic cells, is the major functional consequence of fine-scale base composition variation in the human genome. The selective pressure driving base composition evolution in mammals co