PgmNr D1471: CLAMP: Sex Specific or Global Transcription Factor.

Authors:
W. Jordan; J. Johnson; C. Doherty; E. Larschan


Institutes
Brown University, Providence, RI.


Keyword: translational regulation

Abstract:

Dosage compensation is a mechanism by which gene dosage of X-linked genes between males and females is equalized.  In Drosophila, the Male Specific Lethal Complex (MSL) regulates this process. This complex is responsible for the upregulation of a single X-chromosome in males (XY) so that expression of male X chromosome genes is equal to those on the female (XX).  MSL complex also includes two non-coding RNAs called roX (RNA on the X) that are important for targeting of the complex. The protein, Chromatin-Linked Adaptor for MSL Proteins, CLAMP, is directly responsible for mediating the interaction between MSL and DNA elements called MSL Recognition Elements (MRE) that are two-fold enriched on the X chromosome compared with autosomes. While much of what we currently know about CLAMP is in the context of its function during X chromosome dosage compensation, CLAMP is localized to similar MRE-like DNA sequences in all regions of the genome.  Therefore, we used CRISPR to knockout the gene encoding CLAMP to determine how it functions in vivo.  We determined that in the absence of CLAMP males die earlier than females but there are no viable flies of either sex.  Also, CLAMP functions as a repressor of transcription of the roX RNAs in females to assure that aberrant dosage compensation does not occur.  Future experiments include retargeting CLAMP and roX RNAs to determine which factors are sufficient for X chromosome identification.



Flybase Genetic Index:
1. FlyBase gene symbol: Dmel\Clamp; FBgn: FBgn0032979