title: KRAB: a partner for SRY action on chromatin.
abstract: 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.
authors.affiliation: Department of Medicine, VA Medical Center, University of California at San Francisco, 4150 Clement Street, San Francisco, CA 94121, USA.
authors.forename: Hyun Ju
authors.initials: HJ
authors.lastname: Oh
authors.forename: Yun-Fai Chris
authors.initials: YF
authors.lastname: Lau
mesh_terms: 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
chemical_list: 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