The first and last exons in a given gene were not considered, since they could be influenced to a great SCH727965 extent by transcription. RNA-seq reads and ChIP-seq reads of histone modifications as well as RNAPII were then aligned to exons and summed. The sums of reads mapping to exons were divided by the number of base pairs in the associated exon to produce a measurement of expression value and histone modification levels normalized to exon length. A pseudo-count of 0.01 was added to these length-normalized sums. The logarithms of these normalized read counts were taken as the measurements of exon expression and the histone modification intensities on exons. The procedure in was repeated to assess the levels of histone modifications on promoters. ChIP-seq reads of histone modifications were aligned to a window of 4,001 base pairs surrounding the TSS of each gene, and the logarithmic transformation of the read sum was taken as an estimate of the levels of histone modification on the promoters. Furthermore, to examine whether the selected threshold can be expected randomly, we independently permuted the datasets of the histone modification intensities on exons and associated exon expression values to enable that no single data corresponds to the right exon in each dataset. The partial correlation coefficients between different histone modifications and exon expression were calculated based on the generated datasets. The permutation was repeated 100 times, and a distribution of the new pair-wise partial correlations was recalculated for each permutation. The pyruvate dehydrogenase complex plays a pivotal role in glucose metabolism by converting pyruvate to acetyl-CoA and linking the glycolytic pathway with the tricarboxylic acid cycle. Mammalian PDC, a multienzyme mitochondrial complex, is composed of multiple copies of three catalytic components, a noncatalytic component dihydrolipoamide dehydrogenase-binding protein and two regulatory components. Regulation of PDC is exerted by its reversible phosphorylation and dephosphorylation by its specific kinases and phosphates, respectively. All of the catalytic and regulatory subunits are encoded by single copies of autosomal genes with the exception of the a subunit of PDH. In mammals, PDHa is encoded by two genes: an X-linked allele that is expressed in somatic cells and an autosomal, intronless paralogue that is expressed only in post-meiotic spermatogenic cells. 
To allow a high rate of aerobic glucose oxidation, adult mammalian brain maintains a high proportion of PDC in the dephosphorylated form. During the prenatal and early postnatal periods PDC also plays a central role in lipid biosynthesis from glucose in the brain. PDC deficiency is one of major genetic disorders of oxidative metabolism, resulting in congenital lactic acidosis and extremely heterogeneous clinical manifestations, which are limited largely to the central nervous system. The large TWS119 company majority of all reported PDC deficiency cases involve defects in the subunit of the PDH component of the complex. More than 371 cases of PDC deficiency have been reported and more than 80% of these cases involve defects in PDH. Various congenital cerebral malformations and neurological dysfunctions have been reported in affected patients. These may range from mild ataxia to profound psychomotor retardation and even early postnatal death. Gross congenital brain malformations have been described in PDC deficiency cases, such as microcephaly, cerebral atrophy and abnormal development of the corpus callosum and pyramids. Because of the location of PDHA1 on the X chromosome, affected males and females manifest the disease differently. Male patients usually develop severe systemic lactic acidosis and neural defects that lead to lethality during early childhood.