頭對頭（head to head, h2h）基因常常會同時表現並參與同樣的生物反應，是一種重要的基因庫（genome）特徵。最近有許多關於頭對頭基因的研究，然而，因為調控資料（例如轉錄因子與啟動子結合證據）的取得不易，這些研究著重於序列上的特徵或是演化上的保留性而缺乏調控機制的分析。在本研究中，我們利用酵母菌（Saccharomyces cerevisiae）中具有文獻支持的調控資料，並藉由基因間表現量的相關度與Gene Ontology (GO)中功能註解的相似度，有系統性地研究頭對頭基因的調控機制。
結果指出（1）頭對頭基因對所佔的比例與期望值相差不多，說明頭對頭基因在酵母菌的基因庫中並沒有佔有較多的比例；（2）頭對頭基因間起始密碼子（start codon）的距離大多落在200到800個核苷酸之間，而轉錄起始點（transcription start site, TSS）的距離則大多落在0到600個核苷酸之間；（3）隨著頭對頭基因與轉錄因子交互作用的數量增加，基因的關聯度也跟著增加；（4）頭對頭基因的關聯度會受特定的轉錄因子所影響；（5）沒有TATA盒的頭對頭基因會有較高的關聯度，但變化並不大。
在本篇研究中，我們驗證了先前對於頭對頭基因的知識，同時利用調控證據歸納出許多全新的觀察，使我們更進一步了解這種基因對。另外本研究的分析也可以應用於其他物種來了解這些結果是否是酵母菌特有的調控機制，亦或是生物界共通的調控法則。

Head-to-head (h2h) genes have been shown prone to co-express and participate in the same biological process. Recently there have been many studies of h2h genes. However, because of the difficulty of acquiring regulation data such as the binding evidence between transcription factors (TFs) and promoters, these studies focused on sequential features and evolutionary conservation but lacked analyzing regulation data. In this study, we utilized regulation evidences with literature support to conduct a systematic analysis of h2h genes in Saccharomyces cerevisiae. We assessed association of two genes by the correlation of their expression profiles and by the similarity of their functional annotations in the gene ontology (GO) database.
The experimental results indicate that i) the ratio of h2h genes was close to the expectation in genome, revealing that h2h genes do not prevail in the yeast genome; ii) the distance between the start codons of most h2h genes fell into the range of 200–800 bps and the distance between the transcription start sites (TSSs) of most h2h genes fell into the range of 0–600 bps; iii) more TFs regulating both h2h genes increased the gene association; iv) the association of two h2h genes was affected by specific TFs; v) the association of h2h genes without TATA box was slightly higher than with TATA boxes.
In this work, we confirmed known properties of h2h gene organization and also provided significant new observations. The results can be applied to other genomes to confirm if the observations in this study were limited to S. cerevisiae or universal in other organisms.

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