These cells are generally tetraploid [9] and studies of gene expression and X chromosome dosage protein inhibitor compensation indicate that they are male [10]. As a natural consequence of chromosomal sex determination in Drosophila, females have two X chromosomes and two pairs of autosomes (2X;2A) and males have a single X chromosome (1X;2A) [11]. Therefore, male cells can be thought of as naturally occurring chromosomal aneuploids. The response to altered gene dose probably occurs at multiple levels, but transcription is an early step in the flow of information from the genome and is a likely site for control. For example, X chromosome dosage compensation clearly occurs at the transcriptional level [12] and is exquisitely precise [13]. The Male Specific Lethal (MSL) complex regulates the balanced expression of X chromosomes in wild type 1X;2A male flies.

MSL is composed of at least four major proteins (Msl1, Msl2, Msl3, and Mof) and two non-coding RNAs (RoX1 and RoX2) [11]. Mof is an acetyltransferase responsible for acetylating H4K16 [11],[14],[15]. Mof is highly enriched on the male X chromosome as a component of the MSL complex. However, Mof also associates with a more limited repertoire of autosomal genes independently of MSL [16]. H4K16ac is associated with increased transcription in many systems [17]. Therefore, it is widely believed that this acetylation results in increased expression of the X chromosome [11], although an alternative hypothesis suggests that MSL sequesters Mof from the autosomes to drive down autosome expression [18].

Determining Entinostat which of these mechanisms occurs is complicated by the very nature of sampling experiments when much of the transcriptome is altered. The number of X chromosome transcripts sampled from the transcriptome depends on the relative abundance of the X chromosome and autosome transcripts. The salient feature of both models is balanced X chromosome and autosome expression. While the term dosage compensation is used to describe X chromosome expression, dosage compensation is not restricted to X chromosomes in Drosophila. Autosomes also show significant, but much less precise, dosage compensation at the expression level [13],[19]�C[21], suggesting that there is a general dose response genome-wide. Despite the clear role of MSL in X chromosome dosage compensation, the control system rules for MSL function and the contribution of global compensation mechanisms to the specific case of the X chromosome are poorly understood. There are three basic transcript control mechanisms that could modify the effect of gene dose: buffering, feedback, and feed-forward [22]. Here we define buffering as the passive absorption of gene dose perturbations by inherent system properties.