MLLT3

MLLT3 (MLLT3, Super Elongation Complex Subunit) is a Protein Coding gene. Diseases associated with MLLT3 include Acute Myeloid Leukemia With T(9;11)(P22;Q23) and Leukemia. Among its related pathways are Gene Expression and Formation of HIV elongation complex in the absence of HIV Tat. An important paralog of this gene is MLLT1.

MLLT3

Chromatin reader component of the super elongation complex (SEC), a complex required to increase the catalytic rate of RNA polymerase II transcription by suppressing transient pausing by the polymerase at multiple sites along the DNA (PubMed:20159561, PubMed:20471948, PubMed:25417107, PubMed:27105114, PubMed:27545619).

Specifically recognizes and binds acylated histone H3, with a preference for histone H3 that is crotonylated (PubMed:25417107, PubMed:27105114, PubMed:27545619, PubMed:30374167, PubMed:30385749).

Crotonylation marks active promoters and enhancers and confers resistance to transcriptional repressors (PubMed:25417107, PubMed:27105114, PubMed:27545619).

Recognizes and binds histone H3 crotonylated at 'Lys-9' (H3K9cr), and with slightly lower affinity histone H3 crotonylated at 'Lys-18' (H3K18cr) (PubMed:27105114).

Also recognizes and binds histone H3 acetylated and butyrylated at 'Lys-9' (H3K9ac and H3K9bu, respectively), but with lower affinity than crotonylated histone H3 (PubMed:25417107, PubMed:27105114, PubMed:30385749).

In the SEC complex, MLLT3 is required to recruit the complex to crotonylated histones (PubMed:27105114, PubMed:27545619).

Recruitment of the SEC complex to crotonylated histones promotes recruitment of DOT1L on active chromatin to deposit histone H3 'Lys-79' methylation (H3K79me) (PubMed:25417107).

Plays a key role in hematopoietic stem cell (HSC) maintenance by preserving, rather than confering, HSC stemness (PubMed:31776511).

Acts by binding to the transcription start site of active genes in HSCs and sustaining level of H3K79me2, probably by recruiting DOT1L (PubMed:31776511).

Anterior/posterior pattern specification Source: Ensembl
Chromatin remodeling Source: GO_Central
Gene expression Source: Ensembl
Hematopoietic stem cell differentiation Source: UniProtKB
Histone acetylation Source: GO_Central
Negative regulation of canonical Wnt signaling pathway Source: MGI
Positive regulation of transcription, DNA-templated Source: UniProtKB
Positive regulation of Wnt signaling pathway, planar cell polarity pathway Source: MGI
Regulation of chromatin organization Source: UniProtKB
Regulation of stem cell division Source: UniProtKB
Regulation of transcription by RNA polymerase II Source: GO_Central
Segment specification Source: Ensembl

Nucleus
Other locations
Chromosome
Note: Colocalizes with acylated histone H3 (PubMed:25417107, PubMed:27105114). Colocalizes with histone H3 crotonylated at 'Lys-18' (H3K18cr) (PubMed:27105114).

A chromosomal aberration involving MLLT3 is associated with acute leukemias. Translocation t(9;11)(p22;q23) with KMT2A/MLL1. The result is a rogue activator protein. Fusion protein KMT2A-MLLT3 interacts with MEN1 and PSIP1 (PubMed:22936661, PubMed:25305204).
A chromosomal aberration involving MLLT3 was observed in a patient with neuromotor development delay, cerebellar ataxia and epilepsy. Translocation t(4;9)(q35;p22).