KRAB: a partner for SRY action on chromatin.
The sex determining region Y (SRY/Sry) gene is necessary and sufficient for testis determination and differentiation in mammals. SRY/Sry encodes a putative transcription factor with a high mobility group (HMG) DNA-binding domain. The spatiotemporal regulation of Sry expression suggests that a brief action of SRY in a limited number of progenitor cells (pre-Sertoli cells) before the onset of default ovarian differentiation is sufficient to switch on testicular differentiation. Recent identification and characterization of the Krüppel-associated box only (KRAB-O) protein as an SRY-interacting protein have provided experimental evidence supporting an interesting model for SRY function. In this model, SRY recruits the KRAB-KAP1 (KRAB-associating protein 1) complex as a chromatin modulator, which provides a molecular mechanism of SRY as a transcription factor. Moreover, the sufficiency of a brief action of SRY for testis differentiation can be partly explained by the heritability of KRAB-mediated chromatin remodeling. Although it is currently uncertain whether KRAB-O is the only KRAB protein with which SRY interacts, we hypothesize that KRAB-O or yet-to-be identified KRAB-containing proteins might play various roles in sex determination and gonadal differentiation.
Oh
Hyun Ju
HJ
Department of Medicine, VA Medical Center, University of California at San Francisco, 4150 Clement Street, San Francisco, CA 94121, USA.
Lau
Yun-Fai Chris
YF
D000818:Animals; D002352:Carrier Proteins / Q000502:physiology*; D002454:Cell Differentiation; D002843:Chromatin / Q000502:physiology*; D042002:Chromatin Assembly and Disassembly; D004268:DNA-Binding Proteins / Q000502:physiology*; D005260:Female; D006107:Granulosa Cells / Q000166:cytology / Q000502:physiology; D006801:Humans; D008297:Male; D009687:Nuclear Proteins / Q000502:physiology*; D012097:Repressor Proteins / Q000502:physiology*; D012708:Sertoli Cells / Q000166:cytology / Q000502:physiology; D019849:Sex Determination Processes; D051876:Sex-Determining Region Y Protein / Q000502:physiology*; D013737:Testis / Q000254:growth & development / Q000502:physiology*; D016335:Zinc Fingers
D002352:Carrier Proteins; D002843:Chromatin; D004268:DNA-Binding Proteins; D009687:Nuclear Proteins; D012097:Repressor Proteins; D051876:Sex-Determining Region Y Protein; C422407:ZNF350 protein, human; C477007:Zfp472 protein, rat; C486788:Zfp472 protein, mouse