Title

Ubiquitinated proteins including uH2A on the human and mouse inactive X chromosome: enrichment in gene rich bands

Student Author(s)

Christine Clemson

GSBS Program

MS in Clinical Investigation

UMMS Affiliation

Department of Cell Biology

Date

12-24-2004

Document Type

Article

Medical Subject Headings

Animals; Antibodies, Monoclonal; Cell Line; Chromosomes, Human, X; *Dosage Compensation, Genetic; Down-Regulation; Gene Expression; Histones; Humans; Mice; Mitosis; RNA, Untranslated; Sex Chromatin; Ubiquitins; X Chromosome

Disciplines

Cell Biology | Life Sciences | Medicine and Health Sciences

Abstract

The inactive X chromosome (Xi) forms a heterochromatic structure in the nucleus that is known to have several modifications to specific histones involving acetylation or methylation. Using three different antibodies in four different cell lines, we demonstrate that the Xi in human and mouse cells is highly enriched in ubiquitinated protein(s), much of which is polyubiquitinated. This ubiquitination appears specific for the Xi as it was not observed for centromeres or other regions of heterochromatin. Results using an antibody specific to ubiquitinated H2A provide a clear link between H2A ubiquitination and gene repression, as visualized across an entire inactive chromosome. Interestingly, the ubiquitination of the chromosome persists into mitosis and can be seen in a reproducible banded pattern. This pattern matches that of Xist RNA which forms bands as it detaches from the mitotic X chromosome. Both ubiquitination and Xist RNA appear enriched in gene dense regions and depleted in gene poor bands, but do not correlate with L1 LINE elements which have been suggested as key to X-inactivation. These results provide evidence that ubiquitination along with Xist RNA plays an important role in the formation of facultative heterochromatin during X-inactivation.

Rights and Permissions

Citation: Chromosoma. 2004 Dec;113(6):324-35. Epub 2004 Nov 20. Link to article on publisher's site

Related Resources

Link to Article in PubMed