HSF4

Heat-shock transcription factors (HSFs) activate heat-shock response genes under conditions of heat or other stresses. HSF4 lacks the carboxyl-terminal hydrophobic repeat which is shared among all vertebrate HSFs and has been suggested to be involved in the negative regulation of DNA binding activity. Two alternatively spliced transcripts encoding distinct isoforms and possessing different transcriptional activity have been described. [provided by RefSeq]

heat shock transcription factor 4

Heat-shock transcription factor that specifically binds heat shock promoter elements (HSE) (PubMed:22587838, PubMed:23507146).

Required for denucleation and organelle rupture and degradation that occur during eye lens terminal differentiation, when fiber cells that compose the lens degrade all membrane-bound organelles in order to provide lens with transparency to allow the passage of light (By similarity).

In this process, may regulate denucleation of lens fiber cells in part by activating DNASE2B transcription (By similarity).

May be involved in DNA repair through the transcriptional regulation of RAD51 (PubMed:22587838).

May up-regulate p53/TP53 protein in eye lens fiber cells, possibly through protein stabilization (PubMed:28981088).

In the eye lens, controls the expression of alpha-crystallin B chain/CRYAB and consequently may be involved in the regulation of lysosomal acidification (By similarity).

Isoform HSF4A:
Transcriptional repressor.

Isoform HSF4B:
Transcriptional activator.

Cell development Source: Ensembl
Histone H3-K9 demethylation Source: Ensembl
Lens fiber cell differentiation Source: UniProtKB
Negative regulation of transcription by RNA polymerase II Source: ARUK-UCL
Positive regulation of cell differentiation Source: Ensembl
Positive regulation of cell population proliferation Source: Ensembl
Positive regulation of transcription by RNA polymerase II Source: Ensembl
Regulation of transcription by RNA polymerase II Source: GO_Central
Visual perception Source: Ensembl

Nucleus

Cataract 5, multiple types (CTRCT5):
An opacification of the crystalline lens of the eye that frequently results in visual impairment or blindness. Opacities vary in morphology, are often confined to a portion of the lens, and may be static or progressive. CTRCT5 includes infantile, lamellar, zonular, nuclear, anterior polar, stellate, and Marner-type cataracts, among others. Finger malformation is observed in some kindreds.

Phosphorylated mainly on serine residues. Phosphorylation on Ser-298 promotes sumoylation on Lys-293.
Isoform HSF4B is constitutively sumoylated. Sumoylation represses the transcriptional activity and is promoted by phosphorylation on Ser-298. HSFA is not sumoylated.