X chromosome dosage compensation represents an epigenetic phenomenon where coordinated regulation of a whole chromosome is required to compensate the imbalance of X-linked gene dosage between the sexes. We study this process in placental mammals, where X chromosome dosage compensation occurs through X chromosome inactivation (XCI), which results in the formation and maintenance of the silent nuclear compartment of the inactive X-chromosome (Xi). XCI is an essential developmental process in which roughly a thousand genes are silenced by the non-coding RNA Xist. This process offers the unique opportunity to understand mechanistically how RNA molecules can establish a distinct nuclear compartment. The female-specific mosaicism resulting from random inactivation of one of the two X-chromosomes also impacts human health as it affects the outcome of X-linked diseases. Our recent advances in studying the complex interplay among Xist RNA, interacting proteins, chromatin and transcription will be presented. We will address how a distinct X chromosome dosage compensation process is employed in early human development and how that process compares to the XCI process.