peb-1

Gene Description

Cbr-PEB-1 is a FLYWCH-type zinc finger protein and sequence-specific DNA-binding transcriptional regulator. Its N-terminal DNA-binding domain contains a Cys/His-rich FLYWCH motif (related to Drosophila Mod(mdg4)) that is required for DNA binding and in vivo activity, while a conserved C-terminal domain of otherwise unknown function is required for full activity; both regions contribute to efficient nuclear localization. PEB-1 binds a YDTGCCRW consensus site found in cis-regulatory elements of pharyngeal target genes such as myo-2, and it can modulate their transcription. In the pharynx PEB-1 is co-expressed with the activating transcription factor PHA-4 at overlapping binding sites and can interfere with PHA-4 function, contributing to control of pharyngeal gene expression. PEB-1 is expressed in most pharyngeal cell types (muscle, epithelial, marginal and gland cells) and at lower levels in hypodermis and hindgut, and is required for normal morphogenesis of the pharynx, vulva and hindgut as well as for normal molting and feeding.

Existing Annotations Review

GO Term	Evidence	Action	Reason
GO:0005634 nucleus	IEA GO_REF:0000120	ACCEPT	Summary: Nuclear localization is well supported: PEB-1 is a DNA-binding transcription factor and its C. elegans ortholog localizes to nuclei (dependent in part on the FLYWCH domain). This electronic annotation is concordant with the experimental IDA annotation below and is accepted as a core localization.
GO:0000122 negative regulation of transcription by RNA polymerase II	IEA GO_REF:0000107	KEEP AS NON CORE	Summary: Consistent with the ortholog's documented ability to interfere with/repress activity of the PHA-4 transcriptional activator at overlapping cis-regulatory sites. This electronic ortholog-transfer annotation is biologically plausible but captures only one direction of PEB-1's context-dependent regulatory activity; it is retained as a non-core process annotation since the directionality is context-specific rather than a defining function.
GO:0000978 RNA polymerase II cis-regulatory region sequence-specific DNA binding	IEA GO_REF:0000107	ACCEPT	Summary: Strongly supported: PEB-1 binds a defined YDTGCCRW consensus sequence in cis-regulatory regions of RNA polymerase II target genes (e.g. the myo-2 C183 element), and DNA binding requires the FLYWCH motif. This sequence-specific cis-regulatory DNA binding is a core molecular function of the protein.
GO:0045944 positive regulation of transcription by RNA polymerase II	IEA GO_REF:0000107	KEEP AS NON CORE	Summary: PEB-1's regulatory output is context-dependent and has been described both as cooperative/activating and as interfering with PHA-4 at the myo-2 element, so a positive-regulation role is plausible by ortholog transfer. As with the negative regulation term, the specific direction is context-dependent rather than a defining function, so it is retained as a non-core process annotation.
GO:0005634 nucleus	IDA PMID:15165844 DNA binding and in vivo function of C.elegans PEB-1 require ...	ACCEPT	Summary: Experimental (IDA) evidence supports nuclear localization; the curators report that efficient nuclear localization requires both the FLYWCH motif and the C-terminal domain. Consistent with PEB-1 function as a nuclear DNA-binding transcription factor. Accepted as a core localization.

Core Functions

Sequence-specific DNA-binding transcription factor that binds a YDTGCCRW consensus in RNA polymerase II cis-regulatory elements of pharyngeal target genes and modulates their transcription.

Molecular Function:

DNA-binding transcription factor activity, RNA polymerase II-specific

Supporting Evidence:

PMID:15165844
Analysis of binding sites revealed a YDTGCCRW PEB-1 consensus-binding site, and matches to this consensus are widespread in the C.elegans genome.

FLYWCH-motif-dependent sequence-specific binding to cis-regulatory regions of RNA polymerase II-transcribed target genes (e.g. the myo-2 C183 element).

Molecular Function:

RNA polymerase II cis-regulatory region sequence-specific DNA binding

Cellular Locations:

nucleus