In embryonic stem (ES) cells, plays a crucial role in the differentiation potential, particularly along the neural lineage, regulating gene induction and H3 'Lys-4' methylation at key developmental loci, including that mediated by retinoic acid (By similarity). Does not affect ES cell self-renewal (By similarity). Component or associated component of some histone methyltransferase complexes which regulates transcription through recruitment of those complexes to gene promoters (PubMed:19131338). As part of the MLL1/MLL complex, involved in mono-, di- and trimethylation at 'Lys-4' of histone H3 (PubMed:19556245). Histone H3 'Lys-4' methylation represents a specific tag for epigenetic transcriptional activation (PubMed:19556245). In association with ASH2L and WDR5, stimulates the histone methyltransferase activities of KMT2A, KMT2B, KMT2C, KMT2D, SETD1A and SETD1B (PubMed:22266653, PubMed:21220120). Component of the SET1 complex, at least composed of the catalytic subunit (SETD1A or SETD1B), WDR5, WDR82, RBBP5, ASH2L/ASH2, CXXC1/CFP1, HCFC1 and DPY30 (PubMed:16253997, PubMed:17355966, PubMed:17998332, PubMed:18838538). Core component of several methyltransferase-containing complexes including MLL1/MLL, MLL2/3 (also named ASCOM complex) and MLL4/WBP7 (PubMed:15199122, PubMed:15960975, PubMed:17500065). Each complex is at least composed of ASH2L, RBBP5, WDR5, DPY30, one or more specific histone methyltransferases (KMT2A/MLL1, KMT2D/MLL2, KMT2C/MLL3 and KMT2B/MLL4), and the facultative components PAGR1, BAP18, CHD8, E2F6, HCFC1, HCFC2, HSP70, INO80C, KDM6A, KANSL1, LAS1L, MAX, MCRS1, MEN1, MGA, MYST1/MOF, NCOA6, PAXIP1/PTIP, PELP1, PHF20, PRP31, RING2, RUVB1/TIP49A, RUVB2/TIP49B, SENP3, TAF1, TAF4, TAF6, TAF7, TAF9, TEX10 and alpha- and beta-tubulin (PubMed:14992727, PubMed:15199122, PubMed:15960975, PubMed:17500065). Component of a histone methylation complex composed of at least ZNF335, RBBP5, ASH2L and WDR5; the complex may have histone H3-specific methyltransferase activity, however does not have specificity for 'Lys-4' of histone H3 (PubMed:19131338). Interacts with ZNF335 (PubMed:19131338, PubMed:23178126). Interacts with ASH2L; the interaction is direct (PubMed:19131338, PubMed:19556245, PubMed:21220120). Interacts with WDR5; the interaction is direct (PubMed:19556245, PubMed:21220120). Components of the ZNF335-RBBP5-ASH2L-WDR5 histone methylation complex may associate with components of a nuclear receptor-mediated transcription complex to form a complex at least composed of ZNF335, HCFC1, CCAR2, EMSY, MKI67, RBBP5, ASH2L and WDR5 (PubMed:19131338). Within this complex interacts with EMSY (PubMed:19131338). Found in a complex with RBBP5, ASH2L, DPY30, KMT2A, KMT2D and WDR5 (By similarity). Interacts with SETD1A (PubMed:17998332). Interacts with WDR82 (PubMed:18838538). Ubiquitously expressed.