April Issue of Nature Genetics

[Bill from WA]

Here are some of the interesting subjects covered in the April Issue of Nature Genetics.

Human mutation rate associated with DNA replication timing
John A Stamatoyannopoulos1,4, Ivan Adzhubei2,4, Robert E Thurman1, Gregory V Kryukov2, Sergei M Mirkin3 & Shamil R Sunyaev2

Eukaryotic transcription occurs within a chromatin environment, whose organization has an important regulatory function and is partly encoded in cis by the DNA sequence itself. Here, we examine whether evolutionary changes in gene expression are linked to changes in the DNA-encoded nucleosome organization of promoters. We find that in aerobic yeast species, where cellular respiration genes are active under typical growth conditions, the promoter sequences of these genes encode a relatively open (nucleosome-depleted) chromatin organization. This nucleosome-depleted organization requires only DNA sequence information, is independent of any cofactors and of transcription, and is a general property of growth-related genes. In contrast, in anaerobic yeast species, where cellular respiration genes are relatively inactive under typical growth conditions, respiration gene promoters encode relatively closed (nucleosome-occupied) chromatin organizations. Our results suggest a previously unidentified genetic mechanism underlying phenotypic diversity, consisting of DNA sequence changes that directly alter the DNA-encoded nucleosome organization of promoters.

Many X-linked microRNAs escape meiotic sex chromosome inactivation
Rui Song1,3, Seungil Ro1,3, Jason D Michaels1, Chanjae Park1, John R McCarrey2 & Wei Yan1
Meiotic sex chromosome inactivation (MSCI) during spermatogenesis is characterized by transcriptional silencing of genes on both the X and Y chromosomes in mid-to-late pachytene spermatocytes1. MSCI is believed to result from meiotic silencing of unpaired DNA because the X and Y chromosomes remain largely unpaired throughout first meiotic prophase2. However, unlike X-chromosome inactivation in female embryonic cells, where 25–30% of X-linked structural genes have been reported to escape inactivation3, previous microarray4- and RT-PCR5–based studies of expression of >364 X-linked mRNA-encoding genes during spermatogenesis have failed to reveal any X-linked gene that escapes the silencing effects of MSCI in primary spermatocytes. Here we show that many X-linked miRNAs are transcribed and processed in pachytene spermatocytes. This unprecedented escape from MSCI by these X-linked miRNAs suggests that they may participate in a critical function at this stage of spermatogenesis, including the possibility that they contribute to the process of MSCI itself, or that they may be essential for post-transcriptional regulation of autosomal mRNAs during the late meiotic and early postmeiotic stages of spermatogenesis.
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Intrinsic variability of gene expression encoded in nucleosome positioning sequences
Jung Kyoon Choi1 & Young-Joon Kim1
Variation in gene expression is an essential material for biological diversity among single cells1, 2, 3, individuals4, 5, 6 and populations or species7, 8, 9. Here we show that expression variability is an intrinsic property that persists at those different levels. Each promoter seems to have a unique capacity to respond to external signals that can be environmental, genetic or even stochastic. Our investigation into nucleosome organization of variably responding promoters revealed a commonly positioned nucleosome at a critical regulatory region where most transcription start sites and TATA elements are located, a deviation from typical nucleosome-free status. The nucleotide sequences in this region of variable promoters showed a high propensity for DNA bending and a periodic distribution of particular dinucleotides, encoding preferences for DNA–nucleosome interaction. Variable expression is likely to occur during removal of this nucleosome for gene activation. This is a unique example of how promoter sequences intrinsically encode regulatory flexibility, which is vital for biological processes such as adaptation, development and evolution.
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Bill

[diomed]

What does this mean in layman's terms?

[Bill from WA]

Hi diomed

Hard to put in layman's terms but below are some links that may help. These studies show that there is a lot more going on than the basic mendelism we learned in school. The 50% from the Mom and 50% from the Dad theory has gone out the window. There is so much more happening at a base level than we ever dreamed.

http://www.pnas.org/content/98/20/11376.full.pdf
http://en.wikipedia.org/wiki/Eukaryotic_transcription
http://scienceweek.com/2005/sw051230-4.htm

Bill